Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis

被引：714

作者：

Novershtern, Noa ^{[1
,2
,3
]}

Subramanian, Aravind ^{[1
]}

Lawton, Lee N. ^{[4
]}

Mak, Raymond H. ^{[1
]}

Haining, W. Nicholas ^{[5
]}

McConkey, Marie E. ^{[6
]}

Habib, Naomi ^{[3
]}

Yosef, Nir ^{[1
]}

Chang, Cindy Y. ^{[1
,6
]}

Shay, Tal ^{[1
]}

Frampton, Garrett M. ^{[2
,4
]}

Drake, Adam C. B. ^{[2
,7
]}

Leskov, Ilya ^{[2
,7
]}

Nilsson, Bjorn ^{[1
,6
]}

Preffer, Fred

Dombkowski, David ^{[8
]}

Evans, John W. ^{[5
]}

Liefeld, Ted ^{[1
]}

Smutko, John S. ^{[9
]}

Chen, Jianzhu ^{[2
,7
]}

Friedman, Nir ^{[3
]}

Young, Richard A. ^{[2
,4
]}

Golub, Todd R. ^{[1
,5
,10
]}

Regev, Aviv ^{[1
,2
,10
]}

Ebert, Benjamin L. ^{[1
,5
,6
]}

机构：

[1] Broad Inst, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02140 USA

[3] Hebrew Univ Jerusalem, Sch Comp Sci, IL-91904 Jerusalem, Israel

[4] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Boston, MA 02115 USA

[7] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[8] Massachusetts Gen Hosp, Boston, MA 02114 USA

[9] Nugen Technol, San Carlos, CA 94070 USA

[10] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL | 2011年 / 144卷 / 02期

关键词：

ACUTE MYELOID-LEUKEMIA; EMBRYONIC STEM-CELLS; ERYTHROID-DIFFERENTIATION; EXPRESSION PROFILES; MODULE NETWORKS; T-CELLS; GENE; BINDING; LINE; ERYTHROPOIESIS;

D O I：

10.1016/j.cell.2011.01.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：296 / 309

页数：14

共 56 条

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