Densely interconnected transcriptional circuits control cell states in human hematopoiesis.

Densely interconnected transcriptional circuits control cell states in human hematopoiesis.
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DOI:
10.1016/j.cell.2011.01.004
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发表时间:
2011-01-21
期刊:
影响因子:
64.5
通讯作者:
Ebert BL
Ebert BL
中科院分区:
生物学1区
文献类型:
--
作者:
Novershtern N;Subramanian A;Lawton LN;Mak RH;Haining WN;McConkey ME;Habib N;Yosef N;Chang CY;Shay T;Frampton GM;Drake AC;Leskov I;Nilsson B;Preffer F;Dombkowski D;Evans JW;Liefeld T;Smutko JS;Chen J;Friedman N;Young RA;Golub TR;Regev A;Ebert BL

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While many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. We identified modules of highly co-expressed genes, some of which are restricted to a single lineage, but most are expressed at variable levels across multiple lineages. We found densely interconnected cis-regulatory circuits and a large number of transcription factors that are differentially expressed across hematopoietic states. These findings suggest a more complex regulatory system for hematopoiesis than previously assumed.
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