研究者業績

郷 康広

ゴウ ヤスヒロ  (Yasuhiro Go)

基本情報

所属
兵庫県立大学 大学院 情報科学研究科 教授
自然科学研究機構 生理学研究所 教授(兼任)
(兼任)生命創成探究センター 教授(兼任)
学位
理学(2003年3月 京都大学)

研究者番号
50377123
ORCID ID
 https://orcid.org/0000-0003-4581-0325
J-GLOBAL ID
201201011980172894
researchmap会員ID
B000219683

外部リンク

☆ 名前
郷 康広(ごう やすひろ)

☆ 所属
兵庫県立大学大学院 情報科学研究科・教授
自然科学研究機構 生命創成探究センター 認知ゲノム研究グループ・教授(兼任)
自然科学研究機構 生理学研究所 認知行動発達機構研究部門・教授(兼任)

☆ 連絡先
[兵庫県立大]
650-0047 兵庫県神戸市中央区港島南町7丁目1番28
tel: 078-303-1931
web: https://u-hyogo.info/research/faculty/go/
e-mail: go[at]gsis.u-hyogo.ac.jp

[生命創成探究センター & 生理学研究所]
444-8585 愛知県岡崎市明大寺町字西郷中38
tel: 0564-55-7762
web: http://www.nips.ac.jp/coggen
e-mail: yago[at]nips.ac.jp

☆ 研究内容
1. ヒト精神疾患病態解明のための霊長類モデル動物の開発
2. ヒトの脳進化に関する比較オミックス研究
3. 脳やこころの個性・多様性解明にむけた認知生命情報解析

☆ 経歴
2003年
 京都大学大学院理学研究科生物科学専攻霊長類学系博士後期課程終了(理学博士)
2003年-2006年
 総合研究大学院大学先導科学研究科博士研究員/上級研究員/学振特別研究員(PD)
2006年-2008年
 ハーバード大学進化生物学部リサーチフェロー/学振海外特別研究員
2008年-2010年
 京都大学大学院理学研究科 グローバルCOE特別講座・特定助教
2010年-2013年
 京都大学霊長類研究所 遺伝子情報分野・助教
2013年-2018年
 自然科学研究機構 新分野創成センター ブレインサイエンス研究分野・特任准教授
2018年-2023年
 自然科学研究機構 生命創成探究センター 認知ゲノム科学研究グループ・特任准教授
 総合研究大学院大学 生命科学研究科・特任准教授(併任)
 生理学研究所 認知行動発達機構研究部門・特任准教授(併任)
2023年-現在
 兵庫県立大大学院情報科学研究科・教授
 自然科学研究機構 生命創成探究センター 認知ゲノム科学研究グループ・教授(兼任)
 自然科学研究機構 生理学研究所 認知行動発達機構研究部門・教授(兼任)


委員歴

 11

主要な論文

 63
  • Muneo Yamaguchi, Shintaro Nakao, Mitsuru Arima, Karis Little, Aditi Singh, Iori Wada, Yoshihiro Kaizu, Souska Zandi, Justus G Garweg, Tetsuya Matoba, Wataru Shiraishi, Ryo Yamasaki, Kensuke Shibata, Yasuhiro Go, Tatsuro Ishibashi, Akiyoshi Uemura, Alan W Stitt, Koh-Hei Sonoda
    Diabetologia 2024年7月8日  査読有り
    AIMS/HYPOTHESIS: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies. METHODS: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography. RESULTS: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion. CONCLUSIONS/INTERPRETATION: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.
  • Yukino Shibata, Noriyuki Toji, Hongdi Wang, Yasuhiro Go, Kazuhiro Wada
    Science advances 10(25) eadn3409 2024年6月21日  査読有り
    Learned behavior, a fundamental adaptive trait in fluctuating environments, is shaped by species-specific constraints. This phenomenon is evident in songbirds, which acquire their species-specific songs through vocal learning. To explore the neurogenetic mechanisms underlying species-specific song learning, we generated F1 hybrid songbirds by crossing Taeniopygia guttata with Aidemosyne modesta. These F1 hybrids demonstrate expanded learning capacities, adeptly mimicking songs from both parental species and other heterospecific songs more extensively than their parental counterparts. Despite the conserved size of brain regions and neuron numbers in the neural circuits for song learning and production, single-cell transcriptomics reveals distinctive transcriptional characteristics in the F1 hybrids, especially in vocal-motor projection neurons. These neurons exhibit enrichment for nonadditively expressed genes, particularly those related to ion channel activity and cell adhesion, which are associated with the degree of song learning among F1 individuals. Our findings provide insights into the emergence of altered learning capabilities through hybridization, linked to cell type-specific transcriptional changes.
  • Haruya Yagishita, Yasuhiro Go, Kazuki Okamoto, Nariko Arimura, Yuji Ikegaya, Takuya Sasaki
    Frontiers in Neuroscience 18 2024年4月17日  査読有り
    Hippocampal pyramidal neurons exhibit diverse spike patterns and gene expression profiles. However, their relationships with single neurons are not fully understood. In this study, we designed an electrophysiology-based experimental procedure to identify gene expression profiles using RNA sequencing of single hippocampal pyramidal neurons whose spike patterns were recorded in living mice. This technique involves a sequence of experiments consisting of in vivo juxtacellular recording and labeling, brain slicing, cell collection, and transcriptome analysis. We demonstrated that the expression levels of a subset of genes in individual hippocampal pyramidal neurons were significantly correlated with their spike burstiness, submillisecond-level spike rise times or spike rates, directly measured by in vivo electrophysiological recordings. Because this methodological approach can be applied across a wide range of brain regions, it is expected to contribute to studies on various neuronal heterogeneities to understand how physiological spike patterns are associated with gene expression profiles.
  • Ken-Ichi Dewa, Nariko Arimura, Wataru Kakegawa, Masayuki Itoh, Toma Adachi, Satoshi Miyashita, Yukiko U Inoue, Kento Hizawa, Kei Hori, Natsumi Honjoya, Haruya Yagishita, Shinichiro Taya, Taisuke Miyazaki, Chika Usui, Shoji Tatsumoto, Akiko Tsuzuki, Hirotomo Uetake, Kazuhisa Sakai, Kazuhiro Yamakawa, Takuya Sasaki, Jun Nagai, Yoshiya Kawaguchi, Masaki Sone, Takayoshi Inoue, Yasuhiro Go, Noritaka Ichinohe, Kozo Kaibuchi, Masahiko Watanabe, Schuichi Koizumi, Michisuke Yuzaki, Mikio Hoshino
    Nature communications 15(1) 458-458 2024年2月1日  査読有り
    In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission.
  • Noriyuki Toji, Azusa Sawai, Hongdi Wang, Yu Ji, Rintaro Sugioka, Yasuhiro Go, Kazuhiro Wada
    Proceedings of the National Academy of Sciences 121(3) 2024年1月10日  査読有り
    The development of individuality during learned behavior is a common trait observed across animal species; however, the underlying biological mechanisms remain understood. Similar to human speech, songbirds develop individually unique songs with species-specific traits through vocal learning. In this study, we investigate the developmental and molecular mechanisms underlying individuality in vocal learning by utilizing F 1 hybrid songbirds ( Taeniopygia guttata cross with Taeniopygia bichenovii ), taking an integrating approach combining experimentally controlled systematic song tutoring, unbiased discriminant analysis of song features, and single-cell transcriptomics. When tutoring with songs from both parental species, F 1 hybrid individuals exhibit evident diversity in their acquired songs. Approximately 30% of F 1 hybrids selectively learn either song of the two parental species, while others develop merged songs that combine traits from both species. Vocal acoustic biases during vocal babbling initially appear as individual differences in songs among F 1 juveniles and are maintained through the sensitive period of song vocal learning. These vocal acoustic biases emerge independently of the initial auditory experience of hearing the biological father’s and passive tutored songs. We identify individual differences in transcriptional signatures in a subset of cell types, including the glutamatergic neurons projecting from the cortical vocal output nucleus to the hypoglossal nuclei, which are associated with variations of vocal acoustic features. These findings suggest that a genetically predisposed vocal motor bias serves as the initial origin of individual variation in vocal learning, influencing learning constraints and preferences.
  • Donna M Bond, Oscar Ortega-Recalde, Melanie K Laird, Takashi Hayakawa, Kyle S Richardson, Finlay C B Reese, Bruce Kyle, Brooke E McIsaac-Williams, Bruce C Robertson, Yolanda van Heezik, Amy L Adams, Wei-Shan Chang, Bettina Haase, Jacquelyn Mountcastle, Maximilian Driller, Joanna Collins, Kerstin Howe, Yasuhiro Go, Francoise Thibaud-Nissen, Nicholas C Lister, Paul D Waters, Olivier Fedrigo, Erich D Jarvis, Neil J Gemmell, Alana Alexander, Timothy A Hore
    Nature communications 14(1) 6364-6364 2023年10月17日  査読有り
    Combining genome assembly with population and functional genomics can provide valuable insights to development and evolution, as well as tools for species management. Here, we present a chromosome-level genome assembly of the common brushtail possum (Trichosurus vulpecula), a model marsupial threatened in parts of their native range in Australia, but also a major introduced pest in New Zealand. Functional genomics reveals post-natal activation of chemosensory and metabolic genes, reflecting unique adaptations to altricial birth and delayed weaning, a hallmark of marsupial development. Nuclear and mitochondrial analyses trace New Zealand possums to distinct Australian subspecies, which have subsequently hybridised. This admixture allowed phasing of parental alleles genome-wide, ultimately revealing at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We find that reprogramming of possum germline imprints, and the wider epigenome, is similar to eutherian mammals except onset occurs after birth. Together, this work is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits.
  • Kazunori Yamahira, Kobayashi H, Ryo Kakioka, Montenegro J, Masengi KWA, Okuda N, Nagano AJ, Tanaka R, Naruse K, Tatsumoto S, Yasuhiro Go, Ansai S, Junko Kusumi
    Journal of evolutionary biology 2023年9月22日  査読有り
    Because speciation might have been promoted by ancient introgression from an extinct lineage, it is important to detect the existence of 'ghost introgression' in focal taxa and examine its contribution to their diversification. In this study, we examined possible ghost introgression and its contributions to the diversification of ricefishes of the genus Adrianichthys in Lake Poso, an ancient lake on Sulawesi Island, in which some extinctions are known to have occurred. Population-genomic analysis revealed that two extant Adrianichthys species, A. oophorus and A. poptae are reproductively isolated from each other. Comparisons of demographic models demonstrated that introgression from a ghost population, which diverged from the common ancestor of A. oophorus and A. poptae, is essential for reconstructing the demographic history of Adrianichthys. The best model estimated that the divergence of the ghost population greatly predated the divergence between A. oophorus and A. poptae, and that the ghost population secondarily contacted the two extant species within Lake Poso more recently. Genome scans and simulations detected a greatly divergent locus, which cannot be explained without ghost introgression. This locus was also completely segregated between A. oophorus and A. poptae. These findings suggest that variants that came from a ghost population have contributed to the divergence between A. oophorus and A. poptae, but the large time-lag between their divergence and ghost introgression indicates that the contribution of introgression may be restricted.
  • Kazuo Oshima, Akinari Hinoki, Hiroo Uchida, Yujiro Tanaka, Yusuke Okuno, Yasuhiro Go, Chiyoe Shirota, Takahisa Tainaka, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Aitaro Takimoto, Yoko Kano, Shinichiro Sawa
    Pediatric surgery international 39(1) 179-179 2023年4月11日  査読有り
    PURPOSE: Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. METHODS: Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. RESULTS: In all four cases, major immune cells, such as T cells (15.1-47.7%), B cells (3.1-19.0%), monocytes (16.5-31.2%), macrophages (1.6-17.4%), dendritic cells (2.4-12.2%), and natural killer cells (7.5-12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. CONCLUSION: Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.
  • Ko Ito, Yasuhiro Go, Shoji Tatsumoto, Chika Usui, Yosuke Mizuno, Eiji Ikami, Yuta Isozaki, Michihiko Usui, Takeshi Kajihara, Tetsuya Yoda, Ken-Ichi Inoue, Masahiko Takada, Tsuyoshi Sato
    PloS one 18(1) e0280649 2023年  査読有り
    Both Achilles and masticatory muscle tendons are large load-bearing structures, and excessive mechanical loading leads to hypertrophic changes in these tendons. In the maxillofacial region, hyperplasia of the masticatory muscle tendons and aponeurosis affect muscle extensibility resulting in limited mouth opening. Although gene expression profiles of Achilles and patellar tendons under mechanical strain are well investigated in rodents, the gene expression profile of the masticatory muscle tendons remains unexplored. Herein, we examined the gene expression pattern of masticatory muscle tendons and compared it with that of Achilles tendons under tensile strain conditions in the Japanese macaque Macaca fuscata. Primary tenocytes isolated from the masticatory muscle tendons (temporal tendon and masseter aponeurosis) and Achilles tendons were mechanically loaded using the tensile force and gene expression was analyzed using the next-generation sequencing. In tendons exposed to tensile strain, we identified 1076 differentially expressed genes with a false discovery rate (FDR) < 10-10. To identify genes that are differentially expressed in temporal tendon and masseter aponeurosis, an FDR of < 10-10 was used, whereas the FDR for Achilles tendons was set at > 0.05. Results showed that 147 genes are differentially expressed between temporal tendons and masseter aponeurosis, out of which, 125 human orthologs were identified using the Ensemble database. Eight of these orthologs were related to tendons and among them the expression of the glycoprotein nmb and sphingosine kinase 1 was increased in temporal tendons and masseter aponeurosis following exposure to tensile strain. Moreover, the expression of tubulin beta 3 class III, which promotes cell cycle progression, and septin 9, which promotes cytoskeletal rearrangements, were decreased in stretched Achilles tendon cells and their expression was increased in stretched masseter aponeurosis and temporal tendon cells. In conclusion, cyclic strain differentially affects gene expression in Achilles tendons and tendons of the masticatory muscles.
  • Taihei Ninomiya, Atsushi Noritake, Shoji Tatsumoto, Yasuhiro Go, Masaki Isoda
    Scientific reports 12(1) 16539-16539 2022年10月3日  査読有り
    Cognitive skills and the underlying neural architecture are under the influence of genetics. Cognitive genomics research explores the triadic relationship between genes, brain, and cognition, with its major strategy being genotype-driven. Here we show that an inverse strategy is feasible to identify novel candidate genes for particular neuro-cognitive phenotypes in macaques. Two monkeys, originally involved in separate psychological studies, exhibited learning delay and low levels of social performance monitoring. In one monkey, mirror neurons were fewer compared to controls and mu suppression was absent in the frontal cortex. The other monkey showed heightened visual responsiveness in both frontal cortex and dopamine-rich midbrain, with a lack of inter-areal synchronization. Exome analyses revealed that the two monkeys were most likely cousins and shared variants in MAP2, APOC1, and potentially HTR2C. This phenotype-driven strategy in cognitive genomics provides a useful means to clarify the genetic basis of phenotypic variation and develop macaque models of neuropsychiatric disorders.
  • Norman Chinweike Asogwa, Noriyuki Toji, Ziwei He, Chengru Shao, Yukino Shibata, Shoji Tatsumoto, Hiroe Ishikawa, Yasuhiro Go, Kazuhiro Wada
    The Journal of comparative neurology 530(11) 1966-1991 2022年3月28日  査読有り
    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate fast synaptic transmission and cell signaling, which contribute to learning, memory, and the execution of motor skills. Birdsong is a complex learned motor skill in songbirds. Although the existence of 15 nAChR subunits has been predicted in the avian genome, their expression patterns and potential contributions to song learning and production have not been comprehensively investigated. Here, we cloned all the 15 nAChR subunits (ChrnA1-10, B2-4, D, and G) from the zebra finch brain and investigated the mRNA expression patterns in the neural pathways responsible for the learning and production of birdsong during a critical period of song learning. Although there were no detectable hybridization signals for ChrnA1, A6, A9, and A10, the other 11 nAChR subunits were uniquely expressed in one or more major subdivisions in the song nuclei of the songbird brain. Of these 11 subunits, ChrnA3-5, A7, and B2 were differentially regulated in the song nuclei compared with the surrounding anatomically related regions. ChrnA5 was upregulated during the critical period of song learning in the lateral magnocellular nucleus of the anterior nidopallium. Furthermore, single-cell RNA sequencing revealed ChrnA7 and B2 to be the major subunits expressed in neurons of the vocal motor nuclei HVC and robust nucleus of the arcopallium, indicating the potential existence of ChrnA7-homomeric and ChrnB2-heteromeric nAChRs in limited cell populations. These results suggest that relatively limited types of nAChR subunits provide functional contributions to song learning and production in songbirds.
  • Satoshi Ishishita, Shumpei Kitahara, Mayuko Takahashi, Sakura Iwasaki, Shoji Tatsumoto, Izumi Hara, Yoshiki Kaneko, Keiji Kinoshita, Katsushi Yamaguchi, Akihito Harada, Yasushige Ohmori, Yasuyuki Ohkawa, Yasuhiro Go, Shuji Shigenobu, Yoichi Matsuda, Takayuki Suzuki
    PloS one 17(3) e0265008 2022年  査読有り
    The precursor of heme, protoporphyrin IX (PPIX), accumulates abundantly in the uteri of birds, such as Japanese quail, Coturnix japonica, which has brown-speckled eggshells; however, the molecular basis of PPIX production in the uterus remains largely unknown. Here, we investigated the cause of low PPIX production in a classical Japanese quail mutant exhibiting white eggshells by comparing its gene expression in the uterus with that of the wild type using transcriptome analysis. We also performed genetic linkage analysis to identify the causative genomic region of the white eggshell phenotype. We found that 11 genes, including 5'-aminolevulinate synthase 1 (ALAS1) and hephaestin-like 1 (HEPHL1), were specifically upregulated in the wild-type uterus and downregulated in the mutant. We mapped the 172 kb candidate genomic region on chromosome 6, which contains several genes, including a part of the paired-like homeodomain 3 (PITX3), which encodes a transcription factor. ALAS1, HEPHL1, and PITX3 were expressed in the apical cells of the luminal epithelium and lamina propria cells of the uterine mucosa of the wild-type quail, while their expression levels were downregulated in the cells of the mutant quail. Biochemical analysis using uterine homogenates indicated that the restricted availability of 5'-aminolevulinic acid is the main cause of low PPIX production. These results suggest that uterus-specific transcriptional regulation of heme-biosynthesis-related genes is an evolutionarily acquired mechanism of eggshell pigment production in Japanese quail. Based on these findings, we discussed the molecular basis of PPIX production in the uteri of Japanese quails.
  • Kento Nakai, Takahiro Shiga, Rika Yasuhara, Avijite Kumer Sarkar, Yuka Abe, Shiro Nakamura, Yurie Hoashi, Keisuke Kotani, Shoji Tatsumoto, Hiroe Ishikawa, Yasuhiro Go, Tomio Inoue, Kenji Mishima, Wado Akamatsu, Kazuyoshi Baba
    Scientific reports 11(1) 15437-15437 2021年7月29日  査読有り
    The serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.
  • Rollyn Labuguen, Jumpei Matsumoto, Salvador Blanco Negrete, Hiroshi Nishimaru, Hisao Nishijo, Masahiko Takada, Yasuhiro Go, Ken-ichi Inoue, Tomohiro Shibata
    Frontiers in Behavioral Neuroscience 14 581154-581154 2021年1月18日  査読有り
    <jats:p>Video-based markerless motion capture permits quantification of an animal's pose and motion, with a high spatiotemporal resolution in a naturalistic context, and is a powerful tool for analyzing the relationship between the animal's behaviors and its brain functions. Macaque monkeys are excellent non-human primate models, especially for studying neuroscience. Due to the lack of a dataset allowing training of a deep neural network for the macaque's markerless motion capture in the naturalistic context, it has been challenging to apply this technology for macaques-based studies. In this study, we created MacaquePose, a novel open dataset with manually labeled body part positions (keypoints) for macaques in naturalistic scenes, consisting of &amp;gt;13,000 images. We also validated the application of the dataset by training and evaluating an artificial neural network with the dataset. The results indicated that the keypoint estimation performance of the trained network was close to that of a human-level. The dataset will be instrumental to train/test the neural networks for markerless motion capture of the macaques and developments of the algorithms for the networks, contributing establishment of an innovative platform for behavior analysis for non-human primates for neuroscience and medicine, as well as other fields using macaques as a model organism.</jats:p>
  • Kou Hiraga, Yukiko U. Inoue, Junko Asami, Mayuko Hotta, Yuki Morimoto, Shoji Tatsumoto, Mikio Hoshino, Yasuhiro Go, Takayoshi Inoue
    Communications Biology 3(1) 574-574 2020年12月  査読有り
    Individual cell shape and integrity must precisely be orchestrated during morphogenesis. Here, we determine function of type II cadherins, Cdh6, Cdh8, and Cdh11, whose expression combinatorially demarcates the mouse neural plate/tube. While CRISPR/Cas9-based single type II cadherin mutants show no obvious phenotype, Cdh6/8 double knockout (DKO) mice develop intermingled forebrain/midbrain compartments as these two cadherins' expression opposes at the nascent boundary. Cdh6/8/11 triple, Cdh6/8 or Cdh8/11 DKO mice further cause exencephaly just within the cranial region where mutated cadherins' expression merges. In the Cdh8/11 DKO midbrain, we observe less-constricted apical actin meshwork, ventrally-directed spreading, and occasional hyperproliferation among dorsal neuroepithelial cells as origins for exencephaly. These results provide rigid evidence that, by conferring distinct adhesive codes to each cell, redundant type II cadherins serve essential and shared roles in compartmentalization and neurulation, both of which proceed under the robust control of the number, positioning, constriction, and fluidity of neuroepithelial cells.
  • Takushi Kishida, Mamoru Toda, Yasuhiro Go, Shoji Tatsumoto, Takahide Sasai, Tsutomu Hikida
    Molecular phylogenetics and evolution 155 107005-107005 2020年11月4日  査読有り
    Speciation in the open ocean has long been studied, but it remains largely elusive what factors promote or inhibit speciation in such an open environment. Marine amniotes, which evolved from terrestrial ancestors, provide valuable opportunities for studying speciation in the ocean because of their evident aquatic origins. Sea snakes are phylogenetically related to terrestrial elapid snakes and consist of two monophyletic groups (Hydrophiini and Laticaudini). These two groups migrated from land to water almost at the same time, but species diversities are remarkably different: there are approx. 60 species in 16 genera described for hydrophiins, whereas only eight species in the genus Laticauda are described for laticaudins. Here, we provide a high-quality reference genome assembly of a laticaudin L. colubrina with a scaffold N50 value of 40 Mbp, and focused on laticaudins to consider why they have seldom speciated. We performed whole-genome shotgun sequencing of several species of laticaudins sampled in their southmost (Vanuatu) and northmost (Ryukyu) habitats. Demographic histories of Vanuatu and Ryukyu populations suggest that populations of broadly distributed major species are geographically structured. Each species is genetically clearly distinguished, but there is a considerable amount of gene flow between two sibling species distributed sympatrically in Vanuatu. In addition, inter-species genomic admixture is ubiquitously observed among laticaudins even between phylogenetically distant species. Broad distribution of major species combined with such genetic mixability might have prevented laticaudins from genetic isolation and speciation.
  • Kei Hori, Kunihiko Yamashiro, Taku Nagai, Wei Shan, Saki F Egusa, Kazumi Shimaoka, Hiroshi Kuniishi, Masayuki Sekiguchi, Yasuhiro Go, Shoji Tatsumoto, Mitsuyo Yamada, Reika Shiraishi, Kouta Kanno, Satoshi Miyashita, Asami Sakamoto, Manabu Abe, Kenji Sakimura, Masaki Sone, Kazuhiro Sohya, Hiroshi Kunugi, Keiji Wada, Mitsuhiko Yamada, Kiyofumi Yamada, Mikio Hoshino
    iScience 23(6) 101183-101183 2020年6月26日  査読有り
    Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.
  • Joonas A Autio, Matthew F Glasser, Takayuki Ose, Chad J Donahue, Matteo Bastiani, Masahiro Ohno, Yoshihiko Kawabata, Yuta Urushibata, Katsutoshi Murata, Kantaro Nishigori, Masataka Yamaguchi, Yuki Hori, Atsushi Yoshida, Yasuhiro Go, Timothy S Coalson, Saad Jbabdi, Stamatios N Sotiropoulos, Henry Kennedy, Stephen Smith, David C Van Essen, Takuya Hayashi
    NeuroImage 215 116800-116800 2020年4月8日  査読有り
    Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain.
  • Satoshi Ishishita, Shoji Tatsumoto, Keiji Kinoshita, Mitsuo Nunome, Takayuki Suzuki, Yasuhiro Go, Yoichi Matsuda
    PloS one 15(10) e0240183 2020年  査読有り
    Hybrid incompatibility, such as sterility and inviability, prevents gene flow between closely-related populations as a reproductive isolation barrier. F1 hybrids between chickens and Japanese quail (hereafter, referred to as quail), exhibit a high frequency of developmental arrest at the preprimitive streak stage. To investigate the molecular basis of the developmental arrest at the preprimitive streak stage in chicken-quail F1 hybrid embryos, we investigated chromosomal abnormalities in the hybrid embryos using molecular cytogenetic analysis. In addition, we quantified gene expression in parental species and chicken- and quail-derived allele-specific expression in the hybrids at the early blastoderm and preprimitive streak stages by mRNA sequencing. Subsequently, we compared the directions of change in gene expression, including upregulation, downregulation, or no change, from the early blastoderm stage to the preprimitive streak stage between parental species and their hybrids. Chromosome analysis revealed that the cells of the hybrid embryos contained a fifty-fifty mixture of parental chromosomes, and numerical chromosomal abnormalities were hardly observed in the hybrid cells. Gene expression analysis revealed that a part of the genes that were upregulated from the early blastoderm stage to the preprimitive streak stage in both parental species exhibited no upregulation of both chicken- and quail-derived alleles in the hybrids. GO term enrichment analysis revealed that these misregulated genes are involved in various biological processes, including ribosome-mediated protein synthesis and cell proliferation. Furthermore, the misregulated genes included genes involved in early embryonic development, such as primitive streak formation and gastrulation. These results suggest that numerical chromosomal abnormalities due to a segregation failure does not cause the lethality of chicken-quail hybrid embryos, and that the downregulated expression of the genes that are involved in various biological processes, including translation and primitive streak formation, mainly causes the developmental arrest at the preprimitive streak stage in the hybrids.
  • Takushi Kishida, Yasuhiro Go, Shoji Tatsumoto, Kaori Tatsumi, Shigehiro Kuraku, Mamoru Toda
    Proceedings. Biological sciences 286(1910) 20191828-20191828 2019年9月11日  査読有り
    Marine amniotes, a polyphyletic group, provide an excellent opportunity for studying convergent evolution. Their sense of smell tends to degenerate, but this process has not been explored by comparing fully aquatic species with their amphibious relatives in an evolutionary context. Here, we sequenced the genomes of fully aquatic and amphibious sea snakes and identified repertoires of chemosensory receptor genes involved in olfaction. Snakes possess large numbers of the olfactory receptor (OR) genes and the type-2 vomeronasal receptor (V2R) genes, and expression profiling in the olfactory tissues suggests that snakes use the ORs in the main olfactory system (MOS) and the V2Rs in the vomeronasal system (VNS). The number of OR genes has decreased in sea snakes, and fully aquatic species lost MOS which is responsible for detecting airborne odours. By contrast, sea snakes including fully aquatic species retain a number of V2R genes and a well-developed VNS for smelling underwater. This study suggests that the sense of smell also degenerated in sea snakes, particularly in fully aquatic species, but their residual olfactory capability is distinct from that of other fully aquatic amniotes. Amphibious species show an intermediate status between terrestrial and fully aquatic snakes, implying their importance in understanding the process of aquatic adaptation.
  • Xu C, Li Q, Efimova O, He L, Tatsumoto S, Stepanova V, Oishi T, Udono T, Yamaguchi K, Shigenobu S, Kakita A, Nawa H, Khaitovich P, Go Y
    Genome research 28(8) 1097-1110 2018年6月  査読有り
  • Shoji Tatsumoto, Yasuhiro Go, Kentaro Fukuta, Hideki Noguchi, Takashi Hayakawa, Masaki Tomonaga, Hirohisa Hirai, Tetsuro Matsuzawa, Kiyokazu Agata, Asao Fujiyama
    SCIENTIFIC REPORTS 7(1) 13561-13561 2017年11月  査読有り
    Mutations generate genetic variation and are a major driving force of evolution. Therefore, examining mutation rates and modes are essential for understanding the genetic basis of the physiology and evolution of organisms. Here, we aim to identify germline de novo mutations through the whole-genome surveyance of Mendelian inheritance error sites (MIEs), those not inherited through the Mendelian inheritance manner from either of the parents, using ultra-deep whole genome sequences (&gt;150-fold) from a chimpanzee parent-offspring trio. We identified such 889 MIEs and classified them into four categories based on the pattern of inheritance and the sequence read depth: [i] de novo single nucleotide variants (SNVs), [ii] copy number neutral inherited variants, [iii] hemizygous deletion inherited variants, and [iv] de novo copy number variants (CNVs). From de novo SNV candidates, we estimated a germline de novo SNV mutation rate as 1.48 x 10(-8) per site per generation or 0.62 x 10(-9) per site per year. In summary, this study demonstrates the significance of ultra-deep whole genome sequencing not only for the direct estimation of mutation rates but also for discerning various mutation modes including de novo allelic conversion and de novo CNVs by identifying MIEs through the transmission of genomes from parents to offspring.

MISC

 154
  • Chika Shinoda, Keisuke Kitakaze, Yuya Sasai, So-ichiro Nishioka, Isao Kobayashi, Megumi Sumitani, Ken-ichiro Tatematsu, Tetsuya Iizuka, Akira Harazono, Ai Mitani, Akihisa Kaneko, Masanori Imamura, Takako Miyabe-Nishiwaki, Yasuhiro Go, Yoshie Takeuchi, Teru Mizuno, Kei Kiriyama, Jun Tsukimoto, Satomi Nadanaka, Akiko Ishii-Watabe, Takashi Kinoshita, Hiroshi Kitagawa, Yasuyuki Suzuki, Takao Oishi, Hideki Sezutsu, Kohji Itoh
    Research Square 2024年6月5日  
    Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder (LSD) caused by recessive mutations in the α-L-iduronidase (IDUA) gene. Enzyme replacement therapy (ERT) utilizing terminal mannose 6-phosphate (M6P)-carrying N-glycans attached to therapeutic enzymes produced by mammalian cell lines has been clinically applied to several LSDs. Recent studies suggested an unidentified delivery pathway mediated by sialic acid-containing N-glycans. However, more economical platform development is required to produce large quantities of recombinant enzymes. Transgenic silkworms have been established as low-cost systems for expressing recombinant glycoproteins. Microbial endo-β-N-acetylglucosaminidases (ENGases) enable the transglycosylation of N-glycans to other types. In the present study, we established IDUA transgenic silkworms and purified recombinant human IDUA from cocoons. As M6P- and sialic acid-containing N-glycans were not attached to purified hIDUA, we performed ENGase-mediated transglycosylation to obtain hIDUAs with M6P- and sialic acid-containing N-glycans (neoglyco-hIDUAs). Furthermore, we performed intravenous neoglyco-hIDUA replacement therapy in a Japanese macaque MPS I non-human primate model carrying a homozygous Idua missense mutation and succeeded in improving the clinical symptoms and reducing the urinary glycosaminoglycan (GAG) levels. These glycotechnologies using transgenic silkworms and ENGases are expected to serve as platforms for developing therapeutic glycoproteins.
  • 郷 康広
    生体の科学 75(1) 30-35 2024年2月  
    <文献概要>ヒト遺伝学の中心的な課題は,表現型の個性や多様性の遺伝的基盤を理解することにある。近年のゲノム配列の読み取り技術の進歩により,遺伝性疾患のみならず生活習慣病などを含む様々な疾患の要因となるゲノム・遺伝子の変異が明らかになっている。しかし,われわれが普段から目にする"普通"な表現型のばらつき,つまり"ありふれた個性"の遺伝的基盤に関する研究や理解は疾患のそれに比べて遅れている。本稿では,疾患だけでなく,日常にみられる様々な"ありふれた個性"を生み出すゲノム・遺伝的基盤に関しても概観してみたい。
  • 澤田悠斗, 兼子明久, 鯉江洋, 中山駿矢, 岡本宗裕, 郷康広, 辰本将司, 塚本篤士, 中村紳一朗, 宮部貴子, 揚山直英
    日本実験動物学会総会講演要旨集(Web) 71st 2024年  
  • 郷康広, 郷康広, 郷康広, 野口京子, 臼井千夏, 辰本将司
    霊長類研究 39(Supplement) 2023年  

書籍等出版物

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講演・口頭発表等

 26

共同研究・競争的資金等の研究課題

 31

社会貢献活動

 3

メディア報道

 6