生殖系列発生過程における高次遺伝子発現制御の包括的解析

• Project/Area Number: 15080209
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: 阿部 訓也 The Institute of Physical and Chemical Research, 動物変異動態解析技術開発チーム, チームリーダー (40240915)
• Co-Investigator(Kenkyū-buntansha): 清澤 秀孔 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, 開発研究員 (30295422) ; 三瀬 名丹 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, 開発研究員 (00360644) ; 鵜川 義弘 宮城教育大学, 環境教育実践研究センター, 教授 (20232803)
• Project Period (FY): 2003 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥118,700,000 (Direct Cost: ¥118,700,000); Fiscal Year 2007: ¥23,200,000 (Direct Cost: ¥23,200,000); Fiscal Year 2006: ¥23,500,000 (Direct Cost: ¥23,500,000); Fiscal Year 2005: ¥24,000,000 (Direct Cost: ¥24,000,000); Fiscal Year 2004: ¥24,000,000 (Direct Cost: ¥24,000,000); Fiscal Year 2003: ¥24,000,000 (Direct Cost: ¥24,000,000)
• Keywords: 始原生殖細胞 / 多能性幹細胞 / 遺伝子発現 / エピジェネティク / 生殖細胞分化 / ゲノム再プログラム化 / 生殖細胞 / DNAメチル化 / エピジェネティクス / ES細胞 / EG細胞 / マイクロアレイ / 胚性幹細胞 / EST解析 / マイクロアレイ解析 / 発生分化 / cDNA解析

Research Abstract

哺乳類の初期胚には,将来成体のすべての細胞に分化する能力を持つ多分化能細胞が存在し、ここからES細胞のような胚性幹細胞を樹立することが出来る。これらの胚性多能性細胞と始原生殖細胞(PGC)は発生学的にみて、類似した性質を持つことが示唆されており、両者の類似性、相違点を明確にすることはこれらの細胞で生じるゲノム再プログラム化や生殖細胞分化過程の解明に重要と考えられる。
我々は各発生段階の胚体から純化したPGC、および代表的な幹細胞であるES細胞、PGCから派生したEG細胞、精原細胞由来のGS細胞などの幹細胞、およびES細胞から試験管内で分化したPGC様細胞(in vitro PGC; iPGC)のトランスクリプトームの比較解析を行った。その結果、ES細胞とPGCは有意に異なる発現プロファイルを持つことが分かった。各細胞タイプの発現プロファイルの主成分分析を行ったところ、これらはES細胞に類似したグループとPGCに類似した集団の2つのグループに大別できることが明らかとなった。GS細胞はPGCと非常によく似たプロファイルを有しており、iPGCもPGCのグループに分類された。調べた6つのEG細胞株のうち、5つはES細胞と同様のプロファイルを示したが、興味深いことに雌由来EG細胞株、TMA58GのみがPGCグループに分類され、この細胞株の遺伝子発現、その制御に関与するエピジェネティック状態がPGCに類似していることが示唆された。また、主成分分析の結果を元にして、ES細胞、PGCを特徴づける遺伝子群(signature gene)を同定することに成功した。これらのsignature geneの解析により、EG細胞やiPGCとES細胞、あるいはPGCの共通点、相違点を明らかにすることに成功した。

Research Products

• [Journal Article] Quantitative chemical composition of cortical GABAergic neurons revealed in transgenic Venus-expressing rats. (2008)
  • Author(s): Uematsu, M., et. al.
  • Journal Title: Cerebral Cortex 12 Pages: 315-330
  • Peer Reviewed
• [Journal Article] Dynamic Changes in the Epigenomic State and Nuclear Organization of Differentiating Mouse Embryonic Stem Cells. (2007)
  • Author(s): Kobayakawa, S., et. al.
  • Journal Title: Genes to Cells 12 Pages: 447-460
  • Peer Reviewed
• [Journal Article] The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. (2007)
  • Author(s): Cao, L., et. al.
  • Journal Title: Nat Genet. 12 Pages: 386-390
  • Peer Reviewed
• [Journal Article] Comparative analysis of cis-encoded antisense RNAs in eukaryotes. (2007)
  • Author(s): Numata K., et. al.
  • Journal Title: Gene 392 Pages: 134-141
  • Peer Reviewed
• [Journal Article] X chromosome reactivation initiates in nascent primordial germ cells in mice. (2007)
  • Author(s): Sugimoto, M. and Abe, K.
  • Journal Title: PLoS Genetics 12 Pages: 1309-1317
  • Peer Reviewed
• [Journal Article] Molecular dynamics of heterochromatin protein 1β, HP1β, during mouse preimplantation development. (2007)
  • Author(s): Yamazaki, T., et. al.
  • Journal Title: J. Reprod. Dev. 12 Pages: 1035-1041
  • Peer Reviewed
• [Journal Article] Dynamic Changes in the Epigenomic State and Nuclear Organization of Differentiating Mouse Embryonic Stem Cells. (2007)
  • Author(s): Kobayakawa, S., et al.
  • Journal Title: Genes to Cells (in press)
• [Journal Article] Generation of the mitochondrial bottleneck without the reduction of mtDNA content in mouse female germ cells (2007)
  • Author(s): Cao, L., et al.
  • Journal Title: Nature Genetics (in press)
• [Journal Article] Otoptimized beta-galactosidase staining method for simultaneous detection of endogenous gene expression in early mouse embryos. (2006)
  • Author(s): Kishigami, S., et al.
  • Journal Title: Genesis 44・2 Pages: 57-65
• [Journal Article] Comparison of gene expression in male and female mouse blastocysts revealed imprinting of the x-linked gene, rhox5/pem, at preimplantation stages. (2006)
  • Author(s): Kobayashi, S., et al.
  • Journal Title: Current Biology 16・2 Pages: 166-172
• [Journal Article] Stimulation effect of Dnmt3L on the DNA methylation activity of Dnmt3a2. (2006)
  • Author(s): Suetake I., et al.
  • Journal Title: The Journal of Biochemistry 140・4 Pages: 553-559
• [Journal Article] Control of developmental regulators by Polycomb in human embryonic stem cells. (2006)
  • Author(s): Lee TI, et al.
  • Journal Title: Cell 125・2 Pages: 301-313
• [Journal Article] A novel murine gene, Sickle tail (Skt), linked to the Danforth's short tail (Sd) locus, is required for normal development of the intervertebral disc (2006)
  • Author(s): Semba, K., Araki, K., LI, Z., Abe, K., Yamamura, K., et al.
  • Journal Title: Genetics 172 Pages: 445-456
• [Journal Article] An optimized beta-gal staining method for simultaneous detection of endogenous gene expression in early mouse embryos (2006)
  • Author(s): Kishigami, S., Komatsu, Y., Abe, K., Yamamura, K., Mishina, Y., et al.
  • Journal Title: Genesis 44 Pages: 57-65
• [Journal Article] Comparison of gene expression between male and female mouse blastocysts revealed imprinting of the X-linked gene, Rhox5/Pem at preimplantation stages (2006)
  • Author(s): Kobayashi, S., Isotani, A., Mise, N., Abe, K., Okabe, M., et al.
  • Journal Title: Current Biology 16 Pages: 166-172
• [Journal Article] Birth of Mice Produced by Germ Cell Nuclear Transfer (2005)
  • Author(s): Miki, H., Mise, N., Abe, K., Ishino, F., Ogura, A., et al.
  • Journal Title: Genesis 41 Pages: 81-86
• [Journal Article] Disclosing hidden transcripts : mouse natural sense-antisense transcripts tend to be poly(A) negative and nuclear-localized (2005)
  • Author(s): Kiyosawa, K., Mise, N., Iwase S., Hayashizaki, Y., Abe K.
  • Journal Title: Genome Res. 15 Pages: 463-474
• [Journal Article] Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation (2005)
  • Author(s): Yamazaki, H., Sakata, E., Abe, K., Yamamura, K.-I., Kunisada, T., et al.
  • Journal Title: International Immunology 17 Pages: 549-558
  • NAID: 10019359234
• [Journal Article] Birth of Mice Produced by Germ Cell Nuclear Transfer. (2005)
  • Author(s): Miki, H., Inoue, K., Kohda, T., Honda, A., Ogonuki, N., Yuzuriha, M., Mise, N et al.
  • Journal Title: Genesis 41・2 Pages: 81-86
• [Journal Article] Gene content of the 750 kb critical region for mouse embryonic ectoderm lethal tcl-w5. (2004)
  • Author(s): Abe, K., Yuzuriha, M., Sugimoto, M., Ko, M.S.H., Brathwaite, M., Waeltz, P., Nagarra, R.
  • Journal Title: Mammalian Genome 15・4 Pages: 265-276
• [Journal Article] Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. (2004)
  • Author(s): Yoshida, S., Takakura, A., Obbo, K., Abe, K.et al.
  • Journal Title: Developmental Biology 269・2 Pages: 447-458
• [Journal Article] Normal Embryonic and Germ Cell Development in Mice Lacking α1,3-Fucosyltransferase IX (Fut9) Which Show Disappearance of Stage-specific Embryonic Antigen-1 (SSEA-1) (2004)
  • Author(s): Kudo, T., Kaneko, M., Iwasaki, H., Togayachi, A., Nishihara, S., Abe, K., et al.
  • Journal Title: Molecular and Cellular Biology 24・2 Pages: 4221-4228
• [Journal Article] Establishment of an efficient BAC transgenesis protocol and its application to functional characterization of the mouse Brachyury locus. (2004)
  • Author(s): Abe, K., Hazama, M., Katoh, H., Yamamura, K., Suzuki, M.
  • Journal Title: Experimental Animals 53・4 Pages: 311-320
  • NAID: 10013441566
• [Journal Article] Contribution of Asian mouse subspecies Mum musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC end sequence- SNP analysis. (2004)
  • Author(s): Abe, K., Noguchi, H., Tagawa, K., Yuzuriha, M., Toyoda, A et al.
  • Journal Title: Genome Research 14・12 Pages: 2439-2447
• [Presentation] Identification and cloning of embryonic lethal gene, tw5, mapped within the T/t complex of the mouse. (2007)
  • Author(s): Michihiko Sugimoto, et. al.
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
  • Year and Date: 2007-10-30
• [Presentation] Whole genome shotgun sequencing of M. M. molossinus-derived MSM/Ms and detection of vast aomut of SNPs against C57BL/6. (2007)
  • Author(s): Toyoyuki Takada, et. al.
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
  • Year and Date: 2007-10-29
• [Presentation] Which C57BL/6 Substrain is used for the background strain of your mouse? (2007)
  • Author(s): Kazuyuki Mekada, et. al.
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
• [Presentation] Examination of the spatial and temporal expression of sickle tail (SKT) gene in notochordal cells. (2007)
  • Author(s): Kei Semba, et. al.
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
• [Presentation] Mitochondrial bottleneck due to the reduction of mtDNA content in the female germline does not occur in mice. (2007)
  • Author(s): Hiroshi Shitara, et. al.
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
• [Presentation] X chromosome rcactivation initiates in nascent primordial germ cells in mice. (2007)
  • Author(s): Michihiko Sugimoto, Kuniya Abe
  • Organizer: 21st International Mammalian Genomic Conference
  • Place of Presentation: 京都
• [Book] 蛋白質核酸酵素 2007年12月増刊号「生殖細胞の発生・エピジェネティクスと再プログラム化」 (2007)
  • Author(s): 阿部 訓也
  • Total Pages: 205
  • Publisher: 共立出版株式会社
• [Book] 『生物の科学 遺伝』別冊「特集 日本の遺伝学の潮流 日本遺伝学会第78回大会ハイライト」 (2007)
  • Author(s): 阿部 訓也
  • Total Pages: 340
  • Publisher: 株式会社エヌ・ティー・エス
• [Book] ライフサイエンス英語類語使い分け辞典 (2006)
  • Author(s): 金子周司, 鵜川義弘, 他5名
  • Total Pages: 509
  • Publisher: 羊土社
• [Publications] Cachaco, A.S., Abe K., et al.: "Knock-in of integrin b1D affects primmary but not secondary myogenesis in mice."Development. 130. 1659-1671 (2003)
• [Publications] Ara, T., Abe K., et al.: "Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-I (SDF-1)."Proceedings of the National Academy of Science of the USA. 100. 5319-5323 (2003)
• [Publications] Ohbo, K., Abe K., et al.: "Identification and characterization of stem cells in prepubertal spermatogenesis in mice."Developmental Biology. 258. 209-225 (2003)
• [Publications] Santagati, F., Abe K., et al.: "Identification of cis-regulatory elements in the mouse Pax9/Nkx2-9 genomic region Implication for evolutionary conserved synteny."Genetics. 165. 235-242 (2003)
• [Publications] Kokubu, C., Abe K., et al.: "Undulated short-tail deletion mutation in the mouse ablates Pax1 and leads to ectopic activation of neighboring Nkx2-2 in domains that normally express Pax1."Genetics. 165. 299-307 (2003)
• [Publications] Li, Z., Abe K., et al.: "Defective smooth muscle development in qkI-deficient mice."Develop.Growth Diff.. 45. 449-462 (2003)
• [Publications] Sugimoto, M., Abe K., et al.: "Tetraploid embryos rescue the early defects of tw5/tw5 mouse embryos."Genesis. 37. 162-171 (2003)
• [Publications] Tsuda, M., Abe K., et al.: "Conserved role of nanos proteins in germ cell development."Science. 301. 1239-1241 (2003)
• [Publications] Abe, K., et al.: "Gene content of the 750 kb critical region for mouse embryonic ectoderm lethal tcl-w5."Mamm.Genome. (in press). (2004)
• [Publications] Mitsunaga, K., Abe K., et al.: "Loss of PGC-specific expression of the orphan nuclear receptor ERR-β results in reduction of germ cell number in mouse embryos."Mech.Dev.. (in press). (2004)
• [Publications] Yoshida, S., Abe K., et al.: "neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis"Dev.Biol.. (in press). (2004)
• [Publications] Kudo, T., Abe K., et al.: "Normal Embryonic and Germ Cell Development in Mice Lacking al,3-Fucosyltransferase IX (Fut9) Which Show Disappearance of Stage-specific Embryonic Antigen-1 (SSEA-1)"Molecular and Cellular Biology. (in press). (2004)
• [Publications] Kiyosawa H, et al.: "Antisense transcripts with FANTOM2 clone set and their implications for gene regulation."Genome Res.. 13. 1324-1334 (2003)
• [Publications] Kiyosawa H, et al.: "Introduction of RIKEN-GenoMapper, mapping viewer system."Genome Res.. 13. 1554-1555 (2003)
• [Publications] Kiyosawa H, et al.: "A systematic genome-wide approach to positional candidate cloning for identification of novel human disease genes."Intern.med.J.. (in press). (2004)
• [Publications] 阿部訓也: "「マウスゲノム解読とその意義」遺伝57巻3号2003年5月号"裳華房. 112(82-86) (2003)