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本帖最后由 细胞海洋 于 2010-5-8 10:52 编辑
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* |8 {5 d* T9 J3 k* x# U胚胎干细胞可以分化为不同组织的细胞,但它在何时分化直到最近才搞清楚。以色列希伯来大学和美国的科学家利用生物芯片确认了老鼠胚胎干细胞的分化方式。研究结果发表于最新一期的《细胞—干细胞》(Cell Stem Cell)杂志上。
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分化为特定组织细胞之前,胚胎干细胞保持了开放和活跃的基因组。这可能正是其成功分化的秘密。一旦基因沉默或表达,这一能力就消失了。或者说,干细胞直到最后一刻,都保留了其变身任何细胞的能力。
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7 M3 G5 ]$ X9 F5 T: K8 i为了揭示分化过程如何发生,研究者建立了第一个检测老鼠全基因组的DNA微矩阵平台。微矩阵是一种可同时探测几千种基因的生物芯片。该研究使用的微矩阵,检测的不仅仅是部分基因,而是整个基因组。- f, i& |& z# r& j- N8 r: g3 t' v
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5 x2 s& e9 f. o6 y j% M1 L7 D科学家使用几百个这样的微矩阵,覆盖了干细胞分化的不同时间点。通过观察这些序列,研究人员描绘出了一张路线图,表明干细胞如何、何时分化;以及基因沉默何时发生。 (来源:科技日报 高博)
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4 o/ Q7 A K! V2 l1 n' k0 o(《细胞—干细胞》(Cell Stem Cell),Vol 2, 437-447, 08 May 2008,Sol Efroni, Eran Meshorer)
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v1 Y0 l1 d3 j5 ?2 |更多阅读(英文)
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《细胞—干细胞》论文摘要2 x1 K3 ?3 B6 C% K m8 G3 A3 y
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. _& y' P( n5 B' _( ]7 M+ SCell Stem Cell, Vol 2, 437-447, 08 May 2008
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8 a2 s. X$ b: |/ o# bArticleGlobal Transcription in Pluripotent Embryonic Stem CellsSol Efroni,1,8 Radharani Duttagupta,2 Jill Cheng,2,10 Hesam Dehghani,3,11 Daniel J. Hoeppner,4 Chandravanu Dash,5 David P. Bazett-Jones,3 Stuart Le Grice,5 Ronald D.G. McKay,4 Kenneth H. Buetow,1 Thomas R. Gingeras,2 Tom Misteli,7,9, and Eran Meshorer6,8,9, - Q9 P8 e- Q3 B0 F3 B& W/ K$ n
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1 National Cancer Institute Center for Bioinformatics, National Institutes of Health, Rockville, MD 20852, USA2 Affymetrix, Inc., 3380 Central Expressway, Santa Clara, CA 95051, USA3 The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada4 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20852, USA5 National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA6 Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel7 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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Corresponding authorEran Meshorermeshorer@cc.huji.ac.il
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Corresponding authorTom Mistelimistelit@mail.nih.gov
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H% r. r6 B) S( nSummary. ~5 z5 g/ t- W8 d
9 J) C8 I( Y* \The molecular mechanisms underlying pluripotency and lineage specification from embryonic stem cells (ESCs) are largely unclear. Differentiation pathways may be determined by the targeted activation of lineage-specific genes or by selective silencing of genome regions. Here we show that the ESC genome is transcriptionally globally hyperactive and undergoes large-scale silencing as cells differentiate. Normally silent repeat regions are active in ESCs, and tissue-specific genes are sporadically expressed at low levels. Whole-genome tiling arrays demonstrate widespread transcription in coding and noncoding regions in ESCs, whereas the transcriptional landscape becomes more discrete as differentiation proceeds. The transcriptional hyperactivity in ESCs is accompanied by disproportionate expression of chromatin-remodeling genes and the general transcription machinery. We propose that global transcription is a hallmark of pluripotent ESCs, contributing to their plasticity, and that lineage specification is driven by reduction of the transcribed portion of the genome.9 b! d' l7 a! _$ l! N# n" I' V
1 s) j8 E0 d; U* c9 ~; ]Footnotes8 These authors contributed equally to this work.: A/ c$ \/ b3 r+ n
" X: W% v) \1 R# K$ A1 _" Z5 {9 These authors contributed equally to this work as senior authors.
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: Q6 S5 F U; C, L10 Present address: Novartis Institutes for BioMedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.; y3 n2 W: [! h# [
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11 Present address: Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad 91775-1793, Iran.
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4楼原文 感谢tk1504008 提供 |
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