Spa-1 regulates the maintenance and differentiation of human embryonic stem cells.

作者: Young-Jin Lee , Hee-Young Nah , Seok-Ho Hong , Ji-Won Lee , Ilkyung Jeon

DOI: 10.1387/IJDB.072274YL

关键词:

摘要: Human embryonic stem cells (hESCs) are pluripotent, whereby they can proliferate endlessly and differentiate into many different cell types. At the molecular level, little is known of mechanisms underlying their capability for self-renewal differentiation. In present study, we established two new hESC lines (AMC-hES1 AMC-hES2) demonstrated existence a regulator that may be key molecule in dynamics. Spa-1 principal Ras-proximate 1 (Rap1) GTPase-activating protein hematopoietic progenitor regulates Rap1-related signal transduction expressed restrictively human adult tissues (bone marrow, thymus, spleen). To investigate its functions hESCs, examined spa-1 expression profiles during differentiation used RNA interference (RNAi) to downregulate these cells. Our results show undifferentiated hESCs downregulated addition, process passing from mode was regulated by via Rap1/Raf/mitogen-activated kinase kinase/extracellular signal-related signaling. An RNAi vector against (pSUPER.retro.puro) transfected which were seen three germ layers spite being condition. Based on our findings, therefore, it appears involved dynamics, provide fundamental information regarding hESCs.

参考文章(60)
S.J. Cook, B. Rubinfeld, I. Albert, F. McCormick, RapV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in Rat-1 fibroblasts. The EMBO Journal. ,vol. 12, pp. 3475- 3485 ,(1993) , 10.1002/J.1460-2075.1993.TB06022.X
Naoki Mochizuki, Yusuke Ohba, Etsuko Kiyokawa, Takeshi Kurata, Takeshi Murakami, Takefumi Ozaki, Akira Kitabatake, Kazuo Nagashima, Michiyuki Matsuda, Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i) Nature. ,vol. 400, pp. 891- 894 ,(1999) , 10.1038/23738
M Hattori, N Tsukamoto, M S Nur-e-Kamal, B Rubinfeld, K Iwai, H Kubota, H Maruta, N Minato, Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase-activating domain that affects cell cycle progression. Molecular and Cellular Biology. ,vol. 15, pp. 552- 560 ,(1995) , 10.1128/MCB.15.1.552
V.E. Papaioannou, B.K. Waters, J. Rossant, Interactions between diploid embryonal carcinoma cells and early embryonic cells Cell Differentiation. ,vol. 15, pp. 175- 179 ,(1984) , 10.1016/0045-6039(84)90071-X
Mark R Vossler, Hong Yao, Randall D York, Ming-Gui Pan, Caroline S Rim, Philip J.S Stork, cAMP Activates MAP Kinase and Elk-1 through a B-Raf- and Rap1-Dependent Pathway Cell. ,vol. 89, pp. 73- 82 ,(1997) , 10.1016/S0092-8674(00)80184-1
Qingshen Gao, Latika Singh, Ajay Kumar, Seetha Srinivasan, David E. Wazer, Vimla Band, Human Papillomavirus Type 16 E6-Induced Degradation of E6TP1 Correlates with Its Ability To Immortalize Human Mammary Epithelial Cells Journal of Virology. ,vol. 75, pp. 4459- 4466 ,(2001) , 10.1128/JVI.75.9.4459-4466.2001
E O'Neill, W Kolch, Conferring specificity on the ubiquitous Raf/MEK signalling pathway British Journal of Cancer. ,vol. 90, pp. 283- 288 ,(2004) , 10.1038/SJ.BJC.6601488
K.F Wong, 11q13 is a Cytogenetically Promiscuous Site in Hematologic Malignancies Cancer Genetics and Cytogenetics. ,vol. 113, pp. 93- 95 ,(1999) , 10.1016/S0165-4608(98)00285-4
Alireza Alavi, John D Hood, Ricardo Frausto, Dwayne G Stupack, David A Cheresh, Role of Raf in Vascular Protection from Distinct Apoptotic Stimuli Science. ,vol. 301, pp. 94- 96 ,(2003) , 10.1126/SCIENCE.1082015