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

[1] Lineage promiscuity and plasticity in hematopoietic development [J].

Akashi, K .

HEMATOPOIETIC STEM CELLS V, 2005, 1044 :125-131

[2] Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses [J].

Amit, Ido ;

Garber, Manuel ;

Chevrier, Nicolas ;

Leite, Ana Paula ;

Donner, Yoni ;

Eisenhaure, Thomas ;

Guttman, Mitchell ;

Grenier, Jennifer K. ;

Li, Weibo ;

Zuk, Or ;

Schubert, Lisa A. ;

Birditt, Brian ;

Shay, Tal ;

Goren, Alon ;

Zhang, Xiaolan ;

Smith, Zachary ;

Deering, Raquel ;

McDonald, Rebecca C. ;

Cabili, Moran ;

Bernstein, Bradley E. ;

Rinn, John L. ;

Meissner, Alex ;

Root, David E. ;

Hacohen, Nir ;

Regev, Aviv .

SCIENCE, 2009, 326 (5950) :257-263

[3] THE SCL GENE-PRODUCT - A POSITIVE REGULATOR OF ERYTHROID-DIFFERENTIATION [J].

APLAN, PD ;

NAKAHARA, K ;

ORKIN, SH ;

KIRSCH, IR .

EMBO JOURNAL, 1992, 11 (11) :4073-4081

[4] ACTIVATION AND EXPRESSION OF THE NUCLEAR FACTORS OF ACTIVATED T-CELLS, NFATP AND NFATC, IN HUMAN NATURAL-KILLER-CELLS - REGULATION UPON CD16 LIGAND-BINDING [J].

ARAMBURU, J ;

AZZONI, L ;

RAO, A ;

PERUSSIA, B .

JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) :801-810

[5] Unraveling the crucial roles of Meis1 in leukemogenesis and normal hematopoiesis [J].

Argiropoulos, Bob ;

Yung, Eric ;

Humphries, R. Keith .

GENES & DEVELOPMENT, 2007, 21 (22) :2845-2849

[6] Differential regulation of Foxo3a target genes in erythropoiesis [J].

Bakker, Walbert J. ;

van Dijk, Thamar B. ;

Parren-van Amelsvoort, Martine ;

Kolbus, Andrea ;

Yamamoto, Kazuo ;

Steinlein, Peter ;

Verhaak, Roel G. W. ;

Mak, Tak W. ;

Beug, Hartmut ;

Lowenberg, Bob ;

von Lindern, Marieke .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (10) :3839-3854

[7] Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses [J].

Bhattacharjee, A ;

Richards, WG ;

Staunton, J ;

Li, C ;

Monti, S ;

Vasa, P ;

Ladd, C ;

Beheshti, J ;

Bueno, R ;

Gillette, M ;

Loda, M ;

Weber, G ;

Mark, EJ ;

Lander, ES ;

Wong, W ;

Johnson, BE ;

Golub, TR ;

Sugarbaker, DJ ;

Meyerson, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13790-13795

[8] Core transcriptional regulatory circuitry in human embryonic stem cells [J].

Boyer, LA ;

Lee, TI ;

Cole, MF ;

Johnstone, SE ;

Levine, SS ;

Zucker, JR ;

Guenther, MG ;

Kumar, RM ;

Murray, HL ;

Jenner, RG ;

Gifford, DK ;

Melton, DA ;

Jaenisch, R ;

Young, RA .

CELL, 2005, 122 (06) :947-956

[9] Metagenes and molecular pattern discovery using matrix factorization [J].

Brunet, JP ;

Tamayo, P ;

Golub, TR ;

Mesirov, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (12) :4164-4169

[10] Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia [J].

Bullinger, L ;

Döhner, K ;

Bair, E ;

Fröhling, S ;

Schlenk, RF ;

Tibshirani, R ;

Döhner, H ;

Pollack, JR .

NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (16) :1605-1616

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