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【bio-news】Cell：完整干细胞图谱
在过去的几年当中，Whitehead生物医学研究所(Whitehead Institute for Biomedical Research）Richard Young实验室的研究人员绘制出了这个调控环路的关键部分，但是这个图谱中仍然缺少一些小RNA分子，即microRNAs。microRNA小分子成为了研究热点，这种RNA生物体内源长度约为 20-23个核苷酸的非编码小RNA，通过与靶mRNA的互补配对而在转录后水平上对基因的表达进行负调控，导致mRNA的降解或翻译抑制。研究发现miRNA在大多数动物和植物的基因调控方面扮演着关键的角色。
由于miRNAs是指导干细胞是否保持原有状态的第二套调控因子，因此在发育中扮演了重要的角色。为了搞清楚miRNAs的作用，Young和他的同事进行了进一步的研究，将干细胞图谱上缺失的这一块“拼图”补上，并将研究成果公布在了最新（8月8日）的Cell杂志上。
在这项研究中，Young等人发现了miRNAs如何参与胚胎干细胞环路图谱中的，并且利用这张图谱，科学家们朝着了解成熟细胞如何重新编程，回到胚胎状态，再分化成其它类型细胞的过程又迈进了一步，也增进了对于癌症及其它疾病中miRNA的作用的了解。
原始出处：
Cell, Vol 134, 521-533, 08 August 2008
Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
Alexander Marson,1,2,5 Stuart S. Levine,1,5 Megan F. Cole,1,2 Garrett M. Frampton,1,2 Tobias Brambrink,1 Sarah Johnstone,1,2 Matthew G. Guenther,1 Wendy K. Johnston,1,3 Marius Wernig,1 Jamie Newman,1,2 J. Mauro Calabrese,2,4 Lucas M. Dennis,1,2 Thomas L. Volkert,1 Sumeet Gupta,1 Jennifer Love,1 Nancy Hannett,1 Phillip A. Sharp,2,4 David P. Bartel,1,2,3 Rudolf Jaenisch,1,2 and Richard A. Young1,2,
1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
3 Howard Hughes Medical Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
4 Koch Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
Corresponding author
Richard A. Young
young@wi.mit.edu
Summary
MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.
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作者:admin@医学,生命科学 2011-03-15 05:14
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