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Densely interconnected transcriptional circuits control cell states in human hematopoiesis

Novershtern, Noa; Subramanian, Aravind; Lawton, Lee N; Mak, Raymond H; Haining, W Nicholas; McConkey, Marie E; Habib, Naomi; Yosef, Nir; Chang, Cindy Y and Shay, Tal, et al. (2011) In Cell 144(2). p.296-309
Abstract

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... (More)

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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@article{a30938f5-fb55-470e-bf3b-d15ca55a148d,
  abstract     = {<p>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.</p>},
  author       = {Novershtern, Noa and Subramanian, Aravind and Lawton, Lee N and Mak, Raymond H and Haining, W Nicholas and McConkey, Marie E and Habib, Naomi and Yosef, Nir and Chang, Cindy Y and Shay, Tal and Frampton, Garrett M and Drake, Adam C B and Leskov, Ilya and Nilsson, Björn and Preffer, Fred and Dombkowski, David and Evans, John W and Liefeld, Ted and Smutko, John S and Chen, Jianzhu and Friedman, Nir and Young, Richard A and Golub, Todd R and Regev, Aviv and Ebert, Benjamin L},
  issn         = {1097-4172},
  keyword      = {Gene Expression Profiling,Gene Expression Regulation,Gene Regulatory Networks,Hematopoiesis,Humans,Transcription Factors,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {296--309},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Densely interconnected transcriptional circuits control cell states in human hematopoiesis},
  url          = {http://dx.doi.org/10.1016/j.cell.2011.01.004},
  volume       = {144},
  year         = {2011},
}