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The role of SMAD4 in human embryonic stem cell self-renewal and stem cell fate

宇晟添加于 2010-6-10 23:28 | 1821 次阅读 | 0 个评论

作者
Avery S, Zafarana G, Gokhale PJ, Andrews PW
摘要
Transforming growth factor (TGF)-beta superfamily proteins play a key role in the regulation of human embryonic stem cells (hESCs). Those of the TGFbeta/activin/nodal branch seem to support self-renewal and pluripotency, whereas those of the bone morphogenic protein (BMP) branch induce differentiation. In contrast to this generalization, we found that hESC remained undifferentiated after knockdown of SMAD4 with inducible short hairpin RNA interference, although the knockdown inhibited TGFbeta signaling and rendered the cells nonresponsive to BMP-induced differentiation. Moreover, the rapid differentiation of hESC after pharmacological inhibition of TGFbeta/activin/nodal receptor signaling was restricted after SMAD4 knockdown. These results suggest that TGFbeta/activin/nodal signaling supports the undifferentiated phenotype of hESC by suppressing BMP activity. During long-term culture, SMAD4 knockdown cell populations became less stable and more permissive to neural induction, a situation that was rescued by re-establishment of SMAD4 expression. These results suggest that SMAD4 is not required for maintenance of the undifferentiated state of hESC, but rather to stabilize that state.
详细资料
- 文献种类:期刊
- 期刊名称: Stem Cells (Dayton, Ohio)
- 期刊缩写: Stem Cells
- 期卷页: 2010年第28卷第5期 863-873页
- 地址: Department of Biomedical Science, Centre for Stem Cell Biology, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom. stuart.avery@imb.a-star.edu.sg
- ISBN: 1066-5099
- 备注:PMID:20235236
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宇晟的文献笔记订阅

Conquer molecular biology!

The gene, protein and cell signaling pathway are so complicate to me.My boss ask me to read this paper.But i felt so troublesome to read it. It made me confused.When I read the abstract, i can not understand the last sentence totally.Then I went through the full text and i wanted to vomit.So many details i can not understand.Maybe I need to incease my molecular biology as soon as possible.

early know this, why must then?

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