1998 Fiscal Year Annual Research Report

全能性幹細胞から破骨細胞増殖、分化機構の全過程の解析

Research Project

Project/Area Number	10670303
Research Institution	Tottori University
Principal Investigator	林眞一鳥取大学, 医学部, 教授 (50208617)
Keywords	ES細胞 / 破骨細胞 / tal-1 / GATA-2 / M-CSF / ODF / OPGL / ストロマ細胞 / 血液幹細胞
Research Abstract	1個の胚性幹(ES)細胞をストロマ細胞株ST2上にまいて、移しかえるといった操作無しに破骨細胞を誘導できるのですべての過程を1個のコロニーの中で継続的に観察できる。また培養条件を途中で変化させることで血液細胞系譜までの分化、未熟血液細胞の増殖、その後の成熟過程を分離して観察できる。この培養系を用いてtal-1,GATA-1,GATA-2,FOG遺伝子破壊ES細胞から破骨細胞誘導を行ったところ、GATA-1,FOG遺伝子破壊ES細胞は正常と同様に誘導が行えた。tal-1遺伝子破壊ES細胞からは破骨細胞を含む如何なる血液細胞系譜も誘導できなかった。GATA-2遺伝子破壊ES細胞からは頻度は激減していたが一旦、破骨細胞系譜にコミットした前駆細胞は正常と同じように増殖し分化した。このことはGATA-2がES細胞の血液細胞系譜への分化決定に関与していること、しかしながらその後の破骨細胞系譜の分化には関与していないことを示している。さらに抗M-CSF受容体阻害抗体、破骨細胞分化因子(ODF/OPGL)の阻害因子OCIFを培養に加えることでtal-1-->GATA・2-->M-CSF-->ODF/OPGLの順に破骨細胞分化に影響を与えることが明らかになった(投稿中)。現在、活性型Notch-1、不活化型SHP-1等をES細胞に導入しこれらの分子の破骨細胞分化に及ぼす影響を検討している。

Research Products

(9 results)

All Other

All Publications (9 results)

[Publications] H.Yamazaki,et al.: "Tooth-specific expression by the regulatory sequences of rat dentin sialoprotein 2 gene in transgenic mice." Biochem.Biophys.Res.Commun.(in press). (1999)
[Publications] Y.Tanio,et al.: "CD9 molecule expressed on stromal cells is involved in osteoclastogenesis." Exp.Hematol.(in press). (1999)
[Publications] S.I.Hayashi,et al.: "Commitment and differentiation to osteoclast lineage from stem cells." Biochem.Cell Biol.(in press). (1999)
[Publications] H.Yamazaki,et al.: "Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I." Oncogene. 17・23. 2955-2960 (1998)
[Publications] T.Kunisada,et al.: "Transgene expression of steel factor in the basal layer of epidermis promotes survival,proliferation,differentiation and migration of melanocyte precursors." Development. 125・15. 2915-2923 (1998)
[Publications] T.Kunisada,et al.: "Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte expression of transgenic stem cell factor." J.Exp.Med.187・10. 1565-1573 (1998)
[Publications] A.Miyamoto,et al.: "Establishment and characterization of pro-B cell lines from motheaten mutant mouse defective in SHP-1 protein tyrosine phosphatase." Immunol.Letters. 63・2. 75-82 (1998)
[Publications] M.Ogawa,et al.: "Flt3/Flk-2 and c-Kit are not essential for the proliferation of B lymphoid progenitor cells in the bone marrow of the adult mouse." Exp.Hematol.26・6. 478-488 (1998)
[Publications] A.Miyamoto,et al.: "Establishment and characterization of an immortal macrophage-like cell line inducible to differentiate to osteoclasts." Biochem.Biophys.Res.Commun.242・3. 703-709 (1998)

1998 Fiscal Year Annual Research Report

全能性幹細胞から破骨細胞増殖、分化機構の全過程の解析

Principal Investigator

林 眞一 鳥取大学, 医学部, 教授 (50208617)

Research Products

[Publications] H.Yamazaki,et al.: "Tooth-specific expression by the regulatory sequences of rat dentin sialoprotein 2 gene in transgenic mice." Biochem.Biophys.Res.Commun.(in press). (1999)

[Publications] Y.Tanio,et al.: "CD9 molecule expressed on stromal cells is involved in osteoclastogenesis." Exp.Hematol.(in press). (1999)

[Publications] S.I.Hayashi,et al.: "Commitment and differentiation to osteoclast lineage from stem cells." Biochem.Cell Biol.(in press). (1999)

[Publications] H.Yamazaki,et al.: "Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I." Oncogene. 17・23. 2955-2960 (1998)

[Publications] T.Kunisada,et al.: "Transgene expression of steel factor in the basal layer of epidermis promotes survival,proliferation,differentiation and migration of melanocyte precursors." Development. 125・15. 2915-2923 (1998)

[Publications] T.Kunisada,et al.: "Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte expression of transgenic stem cell factor." J.Exp.Med.187・10. 1565-1573 (1998)

[Publications] A.Miyamoto,et al.: "Establishment and characterization of pro-B cell lines from motheaten mutant mouse defective in SHP-1 protein tyrosine phosphatase." Immunol.Letters. 63・2. 75-82 (1998)

[Publications] M.Ogawa,et al.: "Flt3/Flk-2 and c-Kit are not essential for the proliferation of B lymphoid progenitor cells in the bone marrow of the adult mouse." Exp.Hematol.26・6. 478-488 (1998)

[Publications] A.Miyamoto,et al.: "Establishment and characterization of an immortal macrophage-like cell line inducible to differentiate to osteoclasts." Biochem.Biophys.Res.Commun.242・3. 703-709 (1998)

林眞一鳥取大学, 医学部, 教授 (50208617)