近日,，哈佛大學(xué)干細(xì)胞研究所(HSCI)的科學(xué)家研究誘導(dǎo)的多能干細(xì)胞取得進(jìn)步。該研究報(bào)告發(fā)表在10月8日Cell Stem Cell雜志網(wǎng)絡(luò)版上,。
目前的iPS細(xì)胞研究中,，將成人的皮膚細(xì)胞重編程轉(zhuǎn)化為胚胎干細(xì)胞狀態(tài)一般需要四個(gè)基因參與。該課題組利用一種小分子化學(xué)物質(zhì)RepSox代替了其中的Sox2和 cMyc基因的功能,，并且RepSox是在該實(shí)驗(yàn)的不同時(shí)間以不同的形式發(fā)揮功能,。由于cMyc是腫瘤促進(jìn)因子(tumor promoter)，利用 cMyc產(chǎn)生的iPS細(xì)胞不能用于人類疾病治療,，因此十分有必要尋找一種不使用cMyc基因的產(chǎn)生iPS細(xì)胞新方法,。
找到一種安全生產(chǎn)iPS細(xì)胞的方法與研究胚胎干細(xì)胞具有同等重要的生物學(xué)意義。因?yàn)橐曰颊咦陨砑?xì)胞重編程產(chǎn)生的細(xì)胞在移植后理論上可以不需要使用免疫抑制藥物,。同樣的,，患者特異性的iPS細(xì)胞還能用于治療心臟損傷或其他個(gè)性化的治療中。
第一作者Justin K. Ichida介紹說,，這項(xiàng)發(fā)現(xiàn)證實(shí)了利用某些化學(xué)藥物針對(duì)某些需要做移植手術(shù)的患者產(chǎn)生更安全的干細(xì)胞的可行性,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Stem Cell, 08 October 2009 doi:10.1016/j.stem.2009.09.012
A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog
Justin K. Ichida1, 3, 6, Joel Blanchard1, 6, Kelvin Lam1, 6, Esther Y. Son1, 2, 3, 5, 6, Julia E. Chung1, 2, 3, Dieter Egli1, 3, Kyle M. Loh1, Ava C. Carter1, 3, Francesco P. Di Giorgio1, 3, Kathryn Koszka1, 3, Danwei Huangfu1, Hidenori Akutsu4, David R. Liu5, Lee L. Rubin1, , and Kevin Eggan1, 2, 3, ,
1 Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
3 Stowers Medical Institute, 1000 East 50th Street. Kansas City, MO 64110, USA
4 Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535
5 Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
The combined activity of three transcription factors can reprogram adult cells into induced pluripotent stem cells (iPSCs). However, the transgenic methods used for delivering reprogramming factors have raised concerns regarding the future utility of the resulting stem cells. These uncertainties could be overcome if each transgenic factor were replaced with a small molecule that either directly activated its expression from the somatic genome or in some way compensated for its activity. To this end, we have used high-content chemical screening to identify small molecules that can replace Sox2 in reprogramming. We show that one of these molecules functions in reprogramming by inhibiting Tgf-β signaling in a stable and trapped intermediate cell type that forms during the process. We find that this inhibition promotes the completion of reprogramming through induction of the transcription factor Nanog.
