|
|
Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0321.
 Previous Article | Table of Contents | Next Article 
Blood, 15 July 2002, Vol. 100, No. 2, pp. 458-466
HEMATOPOIESIS
Runx1 is essential for hematopoietic commitment at the
hemangioblast stage of development in vitro
Georges Lacaud,
Lia Gore,
Marion Kennedy,
Valerie Kouskoff,
Paul Kingsley,
Christopher Hogan,
Leif Carlsson,
Nancy Speck,
James Palis, and
Gordon Keller
From the Carl C. Icahn Institute for Gene Therapy and
Molecular Medicine, Mount Sinai School of Medicine, New York, NY;
Department of Pediatrics, Division of Hematology-Oncology, and the
Division of Medical Oncology, University of Colorado Health Sciences
Center and Children's Hospital, Denver; Department of Pediatrics and
the Center for Human Genetics and Molecular Pediatric Disease,
University of Rochester, NY; Department of Molecular Biology, Umeå
University, Sweden; and Department of Biochemistry, Dartmouth Medical
School, Hanover, NH.
In this report we demonstrate a role for Runx1 (AML1)
at the hemangioblast stage of hematopoietic and endothelial development in embryonic stem (ES) cell-derived embryoid bodies (EBs).
Runx1 is expressed in EBs during the appearance of
precursors with hemangioblast properties, the blast colony-forming
cells (BL-CFCs). Cell sorting studies revealed that all BL-CFCs within
EBs express Runx1. Runx1-deficient EBs
consistently generate 10- to 20-fold fewer blast colonies than
wild-type controls and display a complete block in definitive hematopoiesis. Despite this defect, Runx1 /
EBs and yolk sacs from mutant embryos generate normal numbers of
primitive erythroid precursors. These observations clearly demonstrate
that Runx1 functions early in hematopoietic development, and they support the interpretation that the primitive erythroid lineage is established early by a subset of BL-CFCs that develop in a
Runx1-independent fashion.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Hoogenkamp, M. Lichtinger, H. Krysinska, C. Lancrin, D. Clarke, A. Williamson, L. Mazzarella, R. Ingram, H. Jorgensen, A. Fisher, et al.
Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program
Blood,
July 9, 2009;
114(2):
299 - 309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Perez-Campo, J. Borrow, V. Kouskoff, and G. Lacaud
The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors
Blood,
May 14, 2009;
113(20):
4866 - 4874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. McKinney-Freeman, C. Lengerke, I.-H. Jang, S. Schmitt, Y. Wang, M. Philitas, J. Shea, and G. Q. Daley
Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes
Blood,
May 15, 2008;
111(10):
4944 - 4953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pearson, P. Sroczynska, G. Lacaud, and V. Kouskoff
The stepwise specification of embryonic stem cells to hematopoietic fate is driven by sequential exposure to Bmp4, activin A, bFGF and VEGF
Development,
April 15, 2008;
135(8):
1525 - 1535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yokomizo, K. Hasegawa, H. Ishitobi, M. Osato, M. Ema, Y. Ito, M. Yamamoto, and S. Takahashi
Runx1 is involved in primitive erythropoiesis in the mouse
Blood,
April 15, 2008;
111(8):
4075 - 4080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-R. Landry, S. Kinston, K. Knezevic, M. F.T.R. de Bruijn, N. Wilson, W. T. Nottingham, M. Peitz, F. Edenhofer, J. E. Pimanda, K. Ottersbach, et al.
Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver
Blood,
March 15, 2008;
111(6):
3005 - 3014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. K. Williamson, D. L. Smith, D. Blinco, R. D. Unwin, S. Pearson, C. Wilson, C. Miller, L. Lancashire, G. Lacaud, V. Kouskoff, et al.
Quantitative Proteomics Analysis Demonstrates Post-transcriptional Regulation of Embryonic Stem Cell Differentiation to Hematopoiesis
Mol. Cell. Proteomics,
March 1, 2008;
7(3):
459 - 472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Walmsley, D. Cleaver, and R. Patient
Fibroblast growth factor controls the timing of Scl, Lmo2, and Runx1 expression during embryonic blood development
Blood,
February 1, 2008;
111(3):
1157 - 1166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. T. Nottingham, A. Jarratt, M. Burgess, C. L. Speck, J.-F. Cheng, S. Prabhakar, E. M. Rubin, P.-S. Li, J. Sloane-Stanley, J. Kong-a-San, et al.
Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer
Blood,
December 15, 2007;
110(13):
4188 - 4197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Wang, P. W. Faloon, Z. Tan, Y. Lv, P. Zhang, Y. Ge, H. Deng, and J.-W. Xiong
Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation
Blood,
November 15, 2007;
110(10):
3601 - 3609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. R. Perlingeiro
Endoglin is required for hemangioblast and early hematopoietic development
Development,
August 15, 2007;
134(16):
3041 - 3048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Li, K. K. Sinha, M. A. Hay, C. R. Rinaldi, Y. Saunthararajah, and G. Nucifora
RUNX1-RUNX1 Homodimerization Modulates RUNX1 Activity and Function
J. Biol. Chem.,
May 4, 2007;
282(18):
13542 - 13551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Tober, A. Koniski, K. E. McGrath, R. Vemishetti, R. Emerson, K. K. L. de Mesy-Bentley, R. Waugh, and J. Palis
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis
Blood,
February 15, 2007;
109(4):
1433 - 1441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. T. Fraser, J. Isern, and M. H. Baron
Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression
Blood,
January 1, 2007;
109(1):
343 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. M. Zeigler, D. Sugiyama, M. Chen, Y. Guo, K. M. Downs, and N. A. Speck
The allantois and chorion, when isolated before circulation or chorio-allantoic fusion, have hematopoietic potential
Development,
November 1, 2006;
133(21):
4183 - 4192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, J.-W. Xiong, C. S. Shelley, H. Park, and M. A. Arnaout
The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells
Development,
September 15, 2006;
133(18):
3641 - 3650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liu, L. Carlsson, and T. Grundstrom
Identification of an N-terminal Transactivation Domain of Runx1 That Separates Molecular Function from Global Differentiation Function
J. Biol. Chem.,
September 1, 2006;
281(35):
25659 - 25669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Abe and Y. Sato
Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies.
Genes Cells,
July 1, 2006;
11(7):
719 - 729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Arufe, M. Lu, A. Kubo, G. Keller, T. F. Davies, and R.-Y. Lin
Directed Differentiation of Mouse Embryonic Stem Cells into Thyroid Follicular Cells
Endocrinology,
June 1, 2006;
147(6):
3007 - 3015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Willey, A. Ayuso-Sacido, H. Zhang, S. T. Fraser, K. E. Sahr, M. J. Adlam, M. Kyba, G. Q. Daley, G. Keller, and M. H. Baron
Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor
Blood,
April 15, 2006;
107(8):
3122 - 3130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Olsen, D. L. Stachura, and M. J. Weiss
Designer blood: creating hematopoietic lineages from embryonic stem cells
Blood,
February 15, 2006;
107(4):
1265 - 1275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Taoudi, A. M. Morrison, H. Inoue, R. Gribi, J. Ure, and A. Medvinsky
Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver
Development,
September 15, 2005;
132(18):
4179 - 4191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hirai, I. M Samokhvalov, T. Fujimoto, S. Nishikawa, J. Imanishi, and S.-I. Nishikawa
Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells
Blood,
September 15, 2005;
106(6):
1948 - 1955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Ng, R. P. Davis, L. Azzola, E. G. Stanley, and A. G. Elefanty
Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation
Blood,
September 1, 2005;
106(5):
1601 - 1603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. T. Zambidis, B. Peault, T. S. Park, F. Bunz, and C. I. Civin
Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development
Blood,
August 1, 2005;
106(3):
860 - 870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Biggs, Y. Zhang, L. F. Peterson, M. Garcia, D.-E. Zhang, and A. S. Kraft
Phosphorylation of AML1/RUNX1 Regulates Its Degradation and Nuclear Matrix Association
Mol. Cancer Res.,
July 1, 2005;
3(7):
391 - 401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kubo, V. Chen, M. Kennedy, E. Zahradka, G. Q. Daley, and G. Keller
The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation
Blood,
June 15, 2005;
105(12):
4590 - 4597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Keller
Embryonic stem cell differentiation: emergence of a new era in biology and medicine
Genes & Dev.,
May 15, 2005;
19(10):
1129 - 1155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. W.M. van Hinsbergh and T. J. Rabelink
FGFR1 and the Bloodline of the Vasculature
Arterioscler Thromb Vasc Biol,
May 1, 2005;
25(5):
883 - 886.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. U. Magnusson, R. Ronca, P. Dell'Era, P. Carlstedt, L. Jakobsson, J. Partanen, A. Dimberg, and L. Claesson-Welsh
Fibroblast Growth Factor Receptor-1 Expression Is Required for Hematopoietic but not Endothelial Cell Development
Arterioscler Thromb Vasc Biol,
May 1, 2005;
25(5):
944 - 949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Ng, L. Azzola, K. Sourris, L. Robb, E. G. Stanley, and A. G. Elefanty
The primitive streak gene Mixl1 is required for efficient haematopoiesis and BMP4-induced ventral mesoderm patterning in differentiating ES cells
Development,
March 1, 2005;
132(5):
873 - 884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, J. R. Biggs, and A. S. Kraft
Phorbol Ester Treatment of K562 Cells Regulates the Transcriptional Activity of AML1c through Phosphorylation
J. Biol. Chem.,
December 17, 2004;
279(51):
53116 - 53125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Hadland, S. S. Huppert, J. Kanungo, Y. Xue, R. Jiang, T. Gridley, R. A. Conlon, A. M. Cheng, R. Kopan, and G. D. Longmore
A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development
Blood,
November 15, 2004;
104(10):
3097 - 3105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Ramirez-Bergeron, A. Runge, K. D. C. Dahl, H. J. Fehling, G. Keller, and M. C. Simon
Hypoxia affects mesoderm and enhances hemangioblast specification during early development
Development,
September 15, 2004;
131(18):
4623 - 4634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. K. Anderson, R. Pant, A. L. Miracle, X. Sun, C. A. Luer, C. J. Walsh, J. C. Telfer, G. W. Litman, and E. V. Rothenberg
Evolutionary Origins of Lymphocytes: Ensembles of T Cell and B Cell Transcriptional Regulators in a Cartilaginous Fish
J. Immunol.,
May 15, 2004;
172(10):
5851 - 5860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Bowcock and W. O.C.M. Cookson
The genetics of psoriasis, psoriatic arthritis and atopic dermatitis
Hum. Mol. Genet.,
April 1, 2004;
13(90001):
R43 - 55.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Telfer, E. E. Hedblom, M. K. Anderson, M. N. Laurent, and E. V. Rothenberg
Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes
J. Immunol.,
April 1, 2004;
172(7):
4359 - 4370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Kaufman, R. L. Lewis, E. T. Hanson, R. Auerbach, J. Plendl, and J. A. Thomson
Functional endothelial cells derived from rhesus monkey embryonic stem cells
Blood,
February 15, 2004;
103(4):
1325 - 1332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Lacaud, V. Kouskoff, A. Trumble, S. Schwantz, and G. Keller
Haploinsufficiency of Runx1 results in the acceleration of mesodermal development and hemangioblast specification upon in vitro differentiation of ES cells
Blood,
February 1, 2004;
103(3):
886 - 889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Nobuhisa, M. Takizawa, S. Takaki, H. Inoue, K. Okita, M. Ueno, K. Takatsu, and T. Taga
Regulation of Hematopoietic Development in the Aorta-Gonad-Mesonephros Region Mediated by Lnk Adaptor Protein
Mol. Cell. Biol.,
December 1, 2003;
23(23):
8486 - 8494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Alvarez-Silva, P. Belo-Diabangouaya, J. Salaun, and F. Dieterlen-Lievre
Mouse placenta is a major hematopoietic organ
Development,
November 15, 2003;
130(22):
5437 - 5444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Palis
Putting a Hex on blood and endothelium
Blood,
October 1, 2003;
102(7):
2315 - 2316.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Guo, R. Chan, H. Ramsey, W. Li, X. Xie, W. C. Shelley, J. P. Martinez-Barbera, B. Bort, K. Zaret, M. Yoder, et al.
The homeoprotein Hex is required for hemangioblast differentiation
Blood,
October 1, 2003;
102(7):
2428 - 2435.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ferkowicz, M. Starr, X. Xie, W. Li, S. A. Johnson, W. C. Shelley, P. R. Morrison, and M. C. Yoder
CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo
Development,
September 15, 2003;
130(18):
4393 - 4403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Chan, S. A. Johnson, Y. Li, M. C. Yoder, and G.-S. Feng
A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis
Blood,
September 15, 2003;
102(6):
2074 - 2080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Fehling, G. Lacaud, A. Kubo, M. Kennedy, S. Robertson, G. Keller, and V. Kouskoff
Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation
Development,
September 1, 2003;
130(17):
4217 - 4227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chadwick, L. Wang, L. Li, P. Menendez, B. Murdoch, A. Rouleau, and M. Bhatia
Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells
Blood,
August 1, 2003;
102(3):
906 - 915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kubo and K. Alitalo
The bloody fate of endothelial stem cells
Genes & Dev.,
February 1, 2003;
17(3):
322 - 329.
[Full Text]
[PDF]
|
|
|
|
|
