1994 Fiscal Year Annual Research Report

動物組織細胞の分化の安定化と分化転換の制御機構

Research Project

Project/Area Number	04404004
Research Institution	National Institute for Basic Biology
Principal Investigator	江口吾朗岡崎国立共同研究機構, 基礎生物学研究所, 教授 (80022581)
Co-Investigator(Kenkyū-buntansha)	阿形清和姫路工業大学, 理学部, 助教授 (70167831) 餅井真岡崎国立共同研究機構, 基礎生物学研究所, 助手 (90202358) 児玉隆治岡崎国立共同研究機構, 基礎生物学研究所, 助教授 (90161950)
Keywords	細胞分化 / 分化形質転換(分化転換) / 遺伝子発現調節 / 細胞増殖因子 / 細胞外基質 / 色素上皮細胞 / 水晶体細胞 / 神経細胞
Research Abstract	平成4〜6年度の3年間に亘り、ニワトリ胚及びヒトの色素上皮細胞を主要な研究対象として、その分化形質の安定化と分化転換の機構の解析を進め、下記の成果を納めた。 1.分化した色素上皮細胞が発現しているTGF_B結合蛋白質遺伝子はalternative splicing によって5.0Kbと6.0Kbの二種のmRNAを産生する。前者の最終産物は細胞外に分泌され後者のそれは細胞外基質に結合し、それぞれが色素上皮細胞自身が産生するTGF_Bの機能を調節することで、同細胞の分化状態を制御しており、6.0KbmRNAの産生の抑制が色素上皮細胞の分化転換と直結すること、また、bFGFがその主要な制御因子のひとつであることを明らかにした。さらに、色素上皮細胞は従来知られていない蛋白分解酵素阻害蛋白質を極めて特異的に発現しており、この蛋白質が色素上皮細胞の機能の分化とその安定化とに必須の役割を担っていることも明らかとなり、色素上皮細胞の分化形質発現の安定化及び分化転換の制御因子群の機能的カスケードの実体が文略解明できた。 2.ヒトの色素上皮細胞は、細胞培養条件下で、容易に脱分化細胞の状態を経てレンズ細胞に分化転換しうることを実証した。また、前記の多能的脱分化細胞から4種の安定な細胞株を樹立することに成功し、その1種が神経細胞の特異性をも発現しうることを証明した。この成果は、ヒトの色素上皮細胞にもイモリの細胞と等価の分化転換能が保存されていることをはじめて実証したもので、その学術的意義は非常に大きいと考えられる。 3.神経上皮(neuroectoderm)に由来する眼杯外層は網膜色素上皮細胞と虹彩色素上皮細胞とに分化するが、前者は環境変化に対する感受性が後者に比べて非常に高いことが明らかとなった。この事実に着目し、虹彩色素上皮細胞を用いて従来より格段に有効な分化転換実験系を確立することが可能となつた。このことにより、今後の研究に新しい展望を開くことができた。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Kosaka,J.,Watanabe,K.,Eguchi,G.: "Transdifferentiation of chicken retinal pigmented epithelial cells in serum-free culture" Experimental Eye Research. 55. 261-267 (1992)
[Publications] Imokawa,Y.,Ono,S.,Takeuchi,T.,Eguchi,G.: "Analysis of a unique molecule responsible for regeneration and stabilization of differentiated stated of tissue cells" International Journal of Developmental Biology. 36. 399-405 (1992)
[Publications] Imokawa,Y.,Eguchi,G.: "Expression and distribution of regeneration-responsive molecule during normal development of the newt,Cynops pyrrhogaster" International Journal of Developmental Biology. 36. 407-412 (1992)
[Publications] Sawada,K.,Agata,K.,Eguchi,G.: "Crystallin gene expression in the process of lentoidogenesis in cultures of chick lens epithelial cells" Experimental Eye Research. 55. 879-887 (1992)
[Publications] Mochii,M.,Iio,A.,Yamamoto,H.,Takeuchi,T.,Eguchi,G.: "Isolation and characterization of a chicken tyrosinase cDNA" Pigment Cell Research. 5. 162-167 (1992)
[Publications] Hyuga,M.,Kodama,R.,Eguchi,G.: "Basic Fibroblast Growth Factor as One of the Essential Factors Regulating Lens Transdifferentiation of Pigmented Epithelial Cell" International Journal of Developmental Biology. 37. 319-326 (1993)
[Publications] Agata,K.,Kobayashi,H.,Itoh,Y.,Mochii,M.,Sawada,K.,Eguchi,G.: "Genetic characterization of the multipotent dedifferentiated state of pigmented epithelial cells in vitro" Development. 118. 1025-1030 (1993)
[Publications] Araki,M.,Kodama,R.,Eguchi,G.,Yasujima,M.,Orii,H.,Watanabe,K.: "Retinal differentiation from multipotential pineal cells of the embryonic quail" Neuroscience Research. 18. 63-72 (1993)
[Publications] Sawada,K.,Agata,K.,Yoshiki,A.,Eguchi,G.: "A set of anti-crystallin monoclonal antibodies for detecting lens specificities: -crystallin as a specific maker for detecting lentoidogenesis in cultures of chicken lens epithelial cells" Japanese Journal of Ophthalmology. 37. 355-368 (1993)
[Publications] Orii,H.,Agata,K.,Sawada,K.,Eguchi,G.,Maisel,H.: "Evidence that the chick lens cytoskeletal protein CP49 belongs to the family of intermediate filament proteins" Current Eye Research. 12. 583-588 (1993)
[Publications] Iio,A.,Mochii,M.,Agata,K.,Kodama,R.,Eguchi,G.: "Expression of the retinal pigmented epithelial cell-specific pP344 gene during development of the chicken eye and identification of its product" Developmental Growth and Differentiation. 36. 155-164 (1994)
[Publications] Kodama,R.,Eguchi,G.: "The role of gap junctional cell-to-cell communication is coupled with ded iffernatiafion of retinal pigmented epithelial cells in the course of transdifferentiation into the lens" International Journal of Developmental Biology. 38. 357-364 (1994)
[Publications] Orii,H.,Hyuga,H.,Mochii,M.,Kosaka,J.,Eguchi,G.,Watanabe,K.: "Predominant melanogenesis and lentoidogenesis in vitro from multipotent pineal cells by dimethyl sulfoxide and hexamethylene bisaceta" International Journal of Developmental Biology. 38. 397-404 (1994)
[Publications] Eguchi,G.,Kodama,R.: "Transdifferentiation" Current Opinion of Cell Biology. 5(6). 1023-1028 (1993)
[Publications] Kodama,R.,Eguchi,G.: "Gene regulation and differentiation in vertebrate ocular tissues" Current Opinion in Genetics and Development. 4. 703-708 (1994)
[Publications] Kodama,R.,Eguchi,G.: "From lens regeneration in the newt to vitro transdifferentiation of vertebrate pigmented epithelial cells" Seminars in Cell Biology. 6(in press). (1995)
[Publications] Eguchi,G.: "Progress in Retinal Research 12 (N.N.Osborne and J.Chader,eds.)" Pergamon Press,Oxford, 205-230 (1993)

1994 Fiscal Year Annual Research Report

動物組織細胞の分化の安定化と分化転換の制御機構

Principal Investigator

江口 吾朗 岡崎国立共同研究機構, 基礎生物学研究所, 教授 (80022581)

Research Products

[Publications] Kosaka,J.,Watanabe,K.,Eguchi,G.: "Transdifferentiation of chicken retinal pigmented epithelial cells in serum-free culture" Experimental Eye Research. 55. 261-267 (1992)

[Publications] Imokawa,Y.,Ono,S.,Takeuchi,T.,Eguchi,G.: "Analysis of a unique molecule responsible for regeneration and stabilization of differentiated stated of tissue cells" International Journal of Developmental Biology. 36. 399-405 (1992)

[Publications] Imokawa,Y.,Eguchi,G.: "Expression and distribution of regeneration-responsive molecule during normal development of the newt,Cynops pyrrhogaster" International Journal of Developmental Biology. 36. 407-412 (1992)

[Publications] Sawada,K.,Agata,K.,Eguchi,G.: "Crystallin gene expression in the process of lentoidogenesis in cultures of chick lens epithelial cells" Experimental Eye Research. 55. 879-887 (1992)

[Publications] Mochii,M.,Iio,A.,Yamamoto,H.,Takeuchi,T.,Eguchi,G.: "Isolation and characterization of a chicken tyrosinase cDNA" Pigment Cell Research. 5. 162-167 (1992)

[Publications] Hyuga,M.,Kodama,R.,Eguchi,G.: "Basic Fibroblast Growth Factor as One of the Essential Factors Regulating Lens Transdifferentiation of Pigmented Epithelial Cell" International Journal of Developmental Biology. 37. 319-326 (1993)

[Publications] Agata,K.,Kobayashi,H.,Itoh,Y.,Mochii,M.,Sawada,K.,Eguchi,G.: "Genetic characterization of the multipotent dedifferentiated state of pigmented epithelial cells in vitro" Development. 118. 1025-1030 (1993)

[Publications] Araki,M.,Kodama,R.,Eguchi,G.,Yasujima,M.,Orii,H.,Watanabe,K.: "Retinal differentiation from multipotential pineal cells of the embryonic quail" Neuroscience Research. 18. 63-72 (1993)

[Publications] Sawada,K.,Agata,K.,Yoshiki,A.,Eguchi,G.: "A set of anti-crystallin monoclonal antibodies for detecting lens specificities: -crystallin as a specific maker for detecting lentoidogenesis in cultures of chicken lens epithelial cells" Japanese Journal of Ophthalmology. 37. 355-368 (1993)

[Publications] Orii,H.,Agata,K.,Sawada,K.,Eguchi,G.,Maisel,H.: "Evidence that the chick lens cytoskeletal protein CP49 belongs to the family of intermediate filament proteins" Current Eye Research. 12. 583-588 (1993)

[Publications] Iio,A.,Mochii,M.,Agata,K.,Kodama,R.,Eguchi,G.: "Expression of the retinal pigmented epithelial cell-specific pP344 gene during development of the chicken eye and identification of its product" Developmental Growth and Differentiation. 36. 155-164 (1994)

[Publications] Kodama,R.,Eguchi,G.: "The role of gap junctional cell-to-cell communication is coupled with ded iffernatiafion of retinal pigmented epithelial cells in the course of transdifferentiation into the lens" International Journal of Developmental Biology. 38. 357-364 (1994)

[Publications] Orii,H.,Hyuga,H.,Mochii,M.,Kosaka,J.,Eguchi,G.,Watanabe,K.: "Predominant melanogenesis and lentoidogenesis in vitro from multipotent pineal cells by dimethyl sulfoxide and hexamethylene bisaceta" International Journal of Developmental Biology. 38. 397-404 (1994)

[Publications] Eguchi,G.,Kodama,R.: "Transdifferentiation" Current Opinion of Cell Biology. 5(6). 1023-1028 (1993)

[Publications] Kodama,R.,Eguchi,G.: "Gene regulation and differentiation in vertebrate ocular tissues" Current Opinion in Genetics and Development. 4. 703-708 (1994)

[Publications] Kodama,R.,Eguchi,G.: "From lens regeneration in the newt to vitro transdifferentiation of vertebrate pigmented epithelial cells" Seminars in Cell Biology. 6(in press). (1995)

[Publications] Eguchi,G.: "Progress in Retinal Research 12 (N.N.Osborne and J.Chader,eds.)" Pergamon Press,Oxford, 205-230 (1993)

江口吾朗岡崎国立共同研究機構, 基礎生物学研究所, 教授 (80022581)