Densely interconnected transcriptional circuits control cell states in human hematopoiesis

Though 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...

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Bibliographic Details
Published in:Cell Vol. 144; no. 2; p. 296
Main Authors: Novershtern, Noa, Subramanian, Aravind, Lawton, Lee N, Mak, Raymond H, Haining, W Nicholas, McConkey, Marie E, Habib, Naomi, Yosef, Nir, Chang, Cindy Y, Shay, Tal, Frampton, Garrett M, Drake, Adam C B, Leskov, Ilya, Nilsson, Bjorn, Preffer, Fred, Dombkowski, David, Evans, John W, Liefeld, Ted, Smutko, John S, Chen, Jianzhu, Friedman, Nir, Young, Richard A, Golub, Todd R, Regev, Aviv, Ebert, Benjamin L
Format: Journal Article
Language:English
Published: United States 21.01.2011
Subjects:
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Hematopoiesis
Humans
Transcription Factors - metabolism
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary:Though 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 coexpressed genes, some of which are restricted to a single lineage but most of which 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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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2011.01.004