1994 Fiscal Year Annual Research Report

胚性腫瘍と胚幹細胞の成立と分化の機構

Research Project

Project/Area Number	06281112
Research Institution	Hiroshima University
Principal Investigator	丹羽太貫広島大学, 原爆放射能医学研究所, 教授 (80093293)
Co-Investigator(Kenkyū-buntansha)	佐竹正延東北大学, 加齢医学研究所, 教授 (50178688) 濱田博司東京都臨床医学総合研究所, 化学療法部, 部長 (00208589) 渥美忠男理化学研究所, 筑波研究センター, 研究員 (50151080) 村松喬名古屋大学, 医学部, 教授 (00030891) 秦順一慶応大学, 医学部, 教授 (90051614)
Keywords	胚性腫瘍細胞 / 胚幹細胞 / 発生・分化 / サイトカイン / 転写因子 / Oct-3 / ELP / ミッドカイン
Research Abstract	1.胚性腫瘍細胞と胚幹細胞の分化の方向付け、とりわけ造血系への分化におけるサイトカインの役割について、多くのことが明らかになった。試験管内で発生・分化を再現する系の開発は時代の要請であり、そのためにはこれらの知見は重要なものとなろう。また、ヒト胚性腫瘍細胞の新しい表面抗原が同定された。 2.胚性腫瘍細胞特異的な転写因子のうち、oct-3は生殖細胞と初期胚幹細胞の未分化性に直接関わる重要な遺伝子であることが明らかになった。またOct-3の下流の遺伝子のクローニングもなされた。当初、未分化性を規定する遺伝子と予測されていたELP遺伝子はステロイド産生組織で大変重要な転写因子であり、同様のZfp-57遺伝子は神経発生での重要性が明らかになりつつある。これは、初期胚で用いられている遺伝子制御系が、後期発生や生体での組織分化にも機能していること、生体の転写制御は少数の機構を組み合わせて用いていること、などを示しており、予想外の結果とは言え興味深い。 3.胚性腫瘍細胞や胚幹細胞の分化過程で発言する遺伝子として同定されたPEBP2は、白血病の発症に重要であることが明らかになった。また胚分化の最初に発現してくるEndoA遺伝子に対する転写因子としてクローニングされたElk遺伝子は、癌遺伝子のets遺伝子群に属するものであることが明らかにされた。 4.さらに胚分化過程で発現するmidkineは、中胚葉系組織に対するサイトカインであり、歯芽の発生などの固体の発生・分化や、各種のがんにおける発現など、さまざまな重要な機能を果たしていることが明らかになった。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Morohashi,K.,Niwa,O.,et al.: "Functional difference between Ad4BP and ELP,and their distributions in steroidogenic tissues." Molecul.Endocrin.8. 643-653 (1994)
[Publications] Kotomura,N.,Niwa,O.,et al.: "Repression of retinoic acid-induced transactivation by embryonal long terminal repeat binding protein." J.Biochem.116. 1309-1316 (1994)
[Publications] Ikeshima,H.,Hata,J.,et al: "Spermatocyte-specific transcription by calmodulin gene II promoter in transgenic mice." Mol.Cell.Endocrin.99. 49-53 (1994)
[Publications] Wenk,J.,Hata,J.,et al.: "Glycolipids of germ cell tumors:extended globo-series glycolipids are a hallmark of human embryonal carcinoma cells." Int.J.Cancer. 58. 108-115 (1994)
[Publications] Muramatsu,T.: "The midkine family of growth differentiation factors." Dev.Growth Differ.36. 1-8 (1994)
[Publications] Obama,H.,Muramatsu,T.,et al.: "The midkine (MK) family of growth differentiation factors:structure of a MK-related pseudogene and the evolutional relationships among members of the MK family." J.Biochem.115. 516-522 (1994)
[Publications] Muramatsu,H.,Muramatsu,T.,et al.: "Localization of heparin-binding,neurite outgrowth and antigenic regions in midkine molecule." Biochem.Biophys.Res.Commun.203. 1131-1139 (1994)
[Publications] Atsumi,T.,et al.: "Monolayer culture condition suitable for primitive erythroid cell differentiation of embryonic stem cells in vitro." Develop.Growth Differ.(in press).
[Publications] Okazaki,S.,Setoyama,C.,et al.: "A novel nuclear protein with zinc fingers down-regulated during early mammalian cell differentiation." J.Biol.Chem.269. 6900-6907 (1994)
[Publications] Matsuura,T.,Setoyama,C.,et al.: "Expression of four mutant ornithine transcarbamylase genes in cultured Cos 1 cells relates to clinical phenotypes." Hum.Genet.93. 129-134 (1994)
[Publications] Bae,S.C.,Satake,M.,et al.: "PEBP2 B/mouse AML1 consists of multiple isoforms that posses differential transactivation potentials." Mol.Cell.Biol.14. 3242-3252 (1994)
[Publications] Sakakura,C.,Satake,M.,et al.: "Growth inhibition and induction of differentiation of t(8;21) acute myeloid leukemia cells by the DNA binding domain of PEBP2 and the AML1/MTG8(ETO) specific antisense oligonucleotide." Proc.Natl.Acad.Sci.USA. 91. 11723-11727 (1994)
[Publications] Nozaki,M.,et al.: "The complete sequence of the gene encoding mouse cytokeratin 15." Gene. 138. 197-200 (1994)
[Publications] Fujimura,Y.,Nozaki,M.,et al.: "One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins." Nucl.Acids.Res.22. 613-618 (1994)
[Publications] Miyashita,T.,Nozaki,M.,et al.: "Activation of the mouse cytokeratin A (endo A) gene in teratocarcinoma F9 cells by the histone deacetylase inhibitor Tricho-statin A." FEBS Letter. 353. 225-229 (1994)
[Publications] Era,T.,Ogawa,M.,et al.: "How B-precursor cells are driven to cycle." Immunol.Rev.137. 35-51 (1994)
[Publications] Nishikawa,S.,Ogawa,M.,et al.: "Stromal cell-dependent bone marrow culture with a nearly protein-free define medium." Immunol.Let.40. 163-169 (1994)

1994 Fiscal Year Annual Research Report

胚性腫瘍と胚幹細胞の成立と分化の機構

Principal Investigator

丹羽 太貫 広島大学, 原爆放射能医学研究所, 教授 (80093293)

Research Products

[Publications] Morohashi,K.,Niwa,O.,et al.: "Functional difference between Ad4BP and ELP,and their distributions in steroidogenic tissues." Molecul.Endocrin.8. 643-653 (1994)

[Publications] Kotomura,N.,Niwa,O.,et al.: "Repression of retinoic acid-induced transactivation by embryonal long terminal repeat binding protein." J.Biochem.116. 1309-1316 (1994)

[Publications] Ikeshima,H.,Hata,J.,et al: "Spermatocyte-specific transcription by calmodulin gene II promoter in transgenic mice." Mol.Cell.Endocrin.99. 49-53 (1994)

[Publications] Wenk,J.,Hata,J.,et al.: "Glycolipids of germ cell tumors:extended globo-series glycolipids are a hallmark of human embryonal carcinoma cells." Int.J.Cancer. 58. 108-115 (1994)

[Publications] Muramatsu,T.: "The midkine family of growth differentiation factors." Dev.Growth Differ.36. 1-8 (1994)

[Publications] Obama,H.,Muramatsu,T.,et al.: "The midkine (MK) family of growth differentiation factors:structure of a MK-related pseudogene and the evolutional relationships among members of the MK family." J.Biochem.115. 516-522 (1994)

[Publications] Muramatsu,H.,Muramatsu,T.,et al.: "Localization of heparin-binding,neurite outgrowth and antigenic regions in midkine molecule." Biochem.Biophys.Res.Commun.203. 1131-1139 (1994)

[Publications] Atsumi,T.,et al.: "Monolayer culture condition suitable for primitive erythroid cell differentiation of embryonic stem cells in vitro." Develop.Growth Differ.(in press).

[Publications] Okazaki,S.,Setoyama,C.,et al.: "A novel nuclear protein with zinc fingers down-regulated during early mammalian cell differentiation." J.Biol.Chem.269. 6900-6907 (1994)

[Publications] Matsuura,T.,Setoyama,C.,et al.: "Expression of four mutant ornithine transcarbamylase genes in cultured Cos 1 cells relates to clinical phenotypes." Hum.Genet.93. 129-134 (1994)

[Publications] Bae,S.C.,Satake,M.,et al.: "PEBP2 B/mouse AML1 consists of multiple isoforms that posses differential transactivation potentials." Mol.Cell.Biol.14. 3242-3252 (1994)

[Publications] Sakakura,C.,Satake,M.,et al.: "Growth inhibition and induction of differentiation of t(8;21) acute myeloid leukemia cells by the DNA binding domain of PEBP2 and the AML1/MTG8(ETO) specific antisense oligonucleotide." Proc.Natl.Acad.Sci.USA. 91. 11723-11727 (1994)

[Publications] Nozaki,M.,et al.: "The complete sequence of the gene encoding mouse cytokeratin 15." Gene. 138. 197-200 (1994)

[Publications] Fujimura,Y.,Nozaki,M.,et al.: "One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins." Nucl.Acids.Res.22. 613-618 (1994)

[Publications] Miyashita,T.,Nozaki,M.,et al.: "Activation of the mouse cytokeratin A (endo A) gene in teratocarcinoma F9 cells by the histone deacetylase inhibitor Tricho-statin A." FEBS Letter. 353. 225-229 (1994)

[Publications] Era,T.,Ogawa,M.,et al.: "How B-precursor cells are driven to cycle." Immunol.Rev.137. 35-51 (1994)

[Publications] Nishikawa,S.,Ogawa,M.,et al.: "Stromal cell-dependent bone marrow culture with a nearly protein-free define medium." Immunol.Let.40. 163-169 (1994)

丹羽太貫広島大学, 原爆放射能医学研究所, 教授 (80093293)