2 B7 u' ~$ Y L( L4 v1 a研究人员发现全基因表达谱分析不能区分OSK和OSKT细胞，他们通过全基因组测序分析，染色质免疫沉淀等方法分析了胚胎干细胞种Tbx3的结合位点，结果发现Tbx3能调控多能性相关因子和重组因子，而且与Oct4, Sox2, Nanog和Smad1具有许多相同的下游调控靶标。这说明通过不同方法获得iPS细胞存在差异，因此在进行体外研究之前，需要严格定义iPS细胞。 7 m5 |6 w2 d7 ]& @ 9 j$ T6 a- `4 b+ A新加坡基因组研究所近期也公布了另外的有关干细胞的研究，他们发现了microRNA控制干细胞分化的机制。研究小组的目标是研究microRNA指导干细胞分化调节的机制，尤其是某些影响人类健康的重大疾病的干细胞分化的microRNA调节机制， 比如说，癌症、神经变性疾病、糖尿病和其他疾病。研究小组希望有朝一日这些研究成果都可以用于指导疾病的诊断和治疗。 2 s; Z# b9 F2 o. q ) I9 X+ E/ Y4 G3 f; Q0 p: P研究人员了解到以microRNAs定向以编码区为靶位对细胞具有深刻的调节作用。他们观察到单个的microRNA序列对胚胎干细胞的分化具有强大的调控能力。这一结果令人十分兴奋，这样就可以用microRNA分子来控制干细胞的分化，或是制备新的干细胞。最有趣的是，研究者可通过计算机预测观察细胞分化的过程。. H) i* f g+ R$ G5 N
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Nature 463, 1096-1100 (25 February 2010) | doi:10.1038/nature08735; Received 14 February 2009; Accepted 9 December 2009; Published online 7 February 2010 1 y1 Z& R7 s5 S5 L: U, F) w, ~- i7 V0 A5 P2 O) C5 U3 x
Tbx3 improves the germ-line competency of induced pluripotent stem cells: U1 u/ L; L7 z. Q8 H2 Q6 U$ V
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Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells1. The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies. s9 u2 s' w: L2 _
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3楼原文 感谢Jonathan 提供作者: uyunbilig 时间: 2010-2-27 22:07