|
|
Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1699.
 Previous Article | Table of Contents | Next Article 
Blood, 15 January 2003, Vol. 101, No. 2, pp. 508-516
HEMATOPOIESIS
Expression of CD41 marks the initiation of definitive
hematopoiesis in the mouse embryo
Hanna K. A. Mikkola,
Yuko Fujiwara,
Thorsten M. Schlaeger,
David Traver, and
Stuart H. Orkin
From the Department of Hematology/Oncology, Children's
Hospital; Department of Pediatric Oncology, Dana Farber Cancer
Institute; and Howard Hughes Medical Institute, Boston, MA.
Murine hematopoietic stem cells (HSCs) originate from
mesoderm in a process that requires the transcription factor SCL/Tal1. To define steps in the commitment to blood cell fate, we compared wild-type and SCL / embryonic stem cell differentiation
in vitro and identified CD41 (GpIIb) as the earliest surface marker
missing from SCL/ embryoid bodies (EBs). Culture of
fluorescence-activated cell sorter (FACS) purified cells from
EBs showed that definitive hematopoietic progenitors were highly
enriched in the CD41+ fraction, whereas endothelial cells
developed from CD41 cells. In the mouse embryo,
expression of CD41 was detected in yolk sac blood islands and in
fetal liver. In yolk sac and EBs, the panhematopoietic marker CD45
appeared in a subpopulation of CD41+ cells. However,
multilineage hematopoietic colonies developed not only from
CD45+CD41+ cells but also from
CD45CD41+ cells, suggesting that CD41 rather
than CD45 marks the definitive culture colony-forming unit (CFU-C) at
the embryonic stage. In contrast, fetal liver CFU-C was
CD45+, and only a subfraction expressed CD41, demonstrating
down-regulation of CD41 by the fetal liver stage. In yolk sac and EBs,
CD41 was coexpressed with embryonic HSC markers c-kit and CD34. Sorting for CD41 and c-kit expression resulted in enrichment of definitive hematopoietic progenitors. Furthermore, the CD41+
c-kit+ population was missing from
runx1/AML1/ EBs that lack definitive hematopoiesis.
These results suggest that the expression of CD41, a candidate target
gene of SCL/Tal1, and c-kit define the divergence of definitive
hematopoiesis from endothelial cells during development. Although CD41
is commonly referred to as megakaryocyte-platelet integrin in adult
hematopoiesis, these results implicate a wider role for CD41 during
murine ontogeny.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Gandillet, A. G. Serrano, S. Pearson, M. Lie-A-Ling, G. Lacaud, and V. Kouskoff
Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification
Blood,
November 26, 2009;
114(23):
4813 - 4822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Stumpo, H. E. Broxmeyer, T. Ward, S. Cooper, G. Hangoc, Y. J. Chung, W. C. Shelley, E. K. Richfield, M. K. Ray, M. C. Yoder, et al.
Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis
Blood,
September 17, 2009;
114(12):
2401 - 2410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Klimchenko, M. Mori, A. DiStefano, T. Langlois, F. Larbret, Y. Lecluse, O. Feraud, W. Vainchenker, F. Norol, and N. Debili
A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis
Blood,
August 20, 2009;
114(8):
1506 - 1517.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. T. Chou, E. Khandros, L. C. Bailey, K. E. Nichols, C. R. Vakoc, Y. Yao, Z. Huang, J. D. Crispino, R. C. Hardison, G. A. Blobel, et al.
Graded repression of PU.1/Sfpi1 gene transcription by GATA factors regulates hematopoietic cell fate
Blood,
July 30, 2009;
114(5):
983 - 994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. McKinney-Freeman, O. Naveiras, F. Yates, S. Loewer, M. Philitas, M. Curran, P. J. Park, and G. Q. Daley
Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells
Blood,
July 9, 2009;
114(2):
268 - 278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamane, N. Hosen, H. Yamazaki, and I. L. Weissman
Expression of AA4.1 marks lymphohematopoietic progenitors in early mouse development
PNAS,
June 2, 2009;
106(22):
8953 - 8958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gekas, K. E. Rhodes, L. M. Gereige, H. Helgadottir, R. Ferrari, S. K. Kurdistani, E. Montecino-Rodriguez, R. Bassel-Duby, E. Olson, A. V. Krivtsov, et al.
Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis
Blood,
April 9, 2009;
113(15):
3461 - 3471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Irion, M.C. Nostro, S.J. Kattman, and G.M. Keller
Directed Differentiation of Pluripotent Stem Cells: From Developmental Biology to Therapeutic Applications
Cold Spring Harb Symp Quant Biol,
March 27, 2009;
(2009)
sqb.2008.73.065v1.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Yokota, K. Oritani, S. Butz, K. Kokame, P. W. Kincade, T. Miyata, D. Vestweber, and Y. Kanakura
The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice
Blood,
March 26, 2009;
113(13):
2914 - 2923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-T. Huang and L.I. Zon
Regulation of Stem Cells in the Zebra Fish Hematopoietic System
Cold Spring Harb Symp Quant Biol,
November 6, 2008;
(2008)
sqb.2008.73.029v1.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. S. Coller and S. J. Shattil
The GPIIb/IIIa (integrin {alpha}IIb{beta}3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend
Blood,
October 15, 2008;
112(8):
3011 - 3025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Goldie, J. L. Lucitti, M. E. Dickinson, and K. K. Hirschi
Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis
Blood,
October 15, 2008;
112(8):
3194 - 3204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Valamehr, S. J. Jonas, J. Polleux, R. Qiao, S. Guo, E. H. Gschweng, B. Stiles, K. Kam, T.-J. M. Luo, O. N. Witte, et al.
Hydrophobic surfaces for enhanced differentiation of embryonic stem cell-derived embryoid bodies
PNAS,
September 23, 2008;
105(38):
14459 - 14464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-J. Yoon, B.-K. Koo, R. Song, H.-W. Jeong, J. Shin, Y.-W. Kim, Y.-Y. Kong, and P.-G. Suh
Mind bomb-1 Is Essential for Intraembryonic Hematopoiesis in the Aortic Endothelium and the Subaortic Patches
Mol. Cell. Biol.,
August 1, 2008;
28(15):
4794 - 4804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Y. Bertrand, A. D. Kim, S. Teng, and D. Traver
CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis
Development,
May 15, 2008;
135(10):
1853 - 1862.
[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]
|
|
|
|
|
|
|
X. Zhao, V. Jankovic, A. Gural, G. Huang, A. Pardanani, S. Menendez, J. Zhang, R. Dunne, A. Xiao, H. Erdjument-Bromage, et al.
Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity
Genes & Dev.,
March 1, 2008;
22(5):
640 - 653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Subramanian, S. Hegde, P. Porayette, M. Yon, P. Hankey, and R. F. Paulson
Friend Virus Utilizes the BMP4-Dependent Stress Erythropoiesis Pathway To Induce Erythroleukemia
J. Virol.,
January 1, 2008;
82(1):
382 - 393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Y. Bertrand, A. D. Kim, E. P. Violette, D. L. Stachura, J. L. Cisson, and D. Traver
Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo
Development,
December 1, 2007;
134(23):
4147 - 4156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Frontelo, D. Manwani, M. Galdass, H. Karsunky, F. Lohmann, P. G. Gallagher, and J. J. Bieker
Novel role for EKLF in megakaryocyte lineage commitment
Blood,
December 1, 2007;
110(12):
3871 - 3880.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Astorga and P. Carlsson
Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4
Development,
October 15, 2007;
134(20):
3753 - 3761.
[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]
|
|
|
|
|
|
|
H. K. Bone and M. J. Welham
Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis
J. Cell Sci.,
May 15, 2007;
120(10):
1752 - 1762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kennedy, S. L. D'Souza, M. Lynch-Kattman, S. Schwantz, and G. Keller
Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures
Blood,
April 1, 2007;
109(7):
2679 - 2687.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kim, P. Lerou, A. Yabuuchi, C. Lengerke, K. Ng, J. West, A. Kirby, M. J. Daly, and G. Q. Daley
Histocompatible Embryonic Stem Cells by Parthenogenesis
Science,
January 26, 2007;
315(5811):
482 - 486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bhatia
Hematopoietic Development from Human Embryonic Stem Cells
Hematology,
January 1, 2007;
2007(1):
11 - 16.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Umemoto, M. Yamato, Y. Shiratsuchi, M. Terasawa, J. Yang, K. Nishida, Y. Kobayashi, and T. Okano
Expression of Integrin beta3 Is Correlated to the Properties of Quiescent Hemopoietic Stem Cells Possessing the Side Population Phenotype
J. Immunol.,
December 1, 2006;
177(11):
7733 - 7739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. A. Mikkola and S. H. Orkin
The journey of developing hematopoietic stem cells.
Development,
October 1, 2006;
133(19):
3733 - 3744.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pang, H.-H. Xue, G. Szalai, X. Wang, Y. Wang, D. K. Watson, W. J. Leonard, G. A. Blobel, and M. Poncz
Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins
Blood,
October 1, 2006;
108(7):
2198 - 2206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rolny, I. Nilsson, P. Magnusson, A. Armulik, L. Jakobsson, P. Wentzel, P. Lindblom, J. Norlin, C. Betsholtz, R. Heuchel, et al.
Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation
Blood,
September 15, 2006;
108(6):
1877 - 1886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Vodyanik, J. A. Thomson, and I. I. Slukvin
Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures
Blood,
September 15, 2006;
108(6):
2095 - 2105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Sakamoto, G. Dai, K. Tsujino, K. Hashimoto, X. Huang, T. Fujimoto, M. Mucenski, J. Frampton, and M. Ogawa
Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development
Blood,
August 1, 2006;
108(3):
896 - 903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Kim, S. He, O. H. Yilmaz, M. J. Kiel, and S. J. Morrison
Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors
Blood,
July 15, 2006;
108(2):
737 - 744.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-i. Takayanagi, T. Hiroyama, S. Yamazaki, T. Nakajima, Y. Morita, J. Usui, K. Eto, T. Motohashi, K. Shiomi, K. Keino-Masu, et al.
Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain
Blood,
June 1, 2006;
107(11):
4317 - 4325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yokota, J. Huang, M. Tavian, Y. Nagai, J. Hirose, J.-C. Zuniga-Pflucker, B. Peault, and P. W. Kincade
Tracing the first waves of lymphopoiesis in mice
Development,
May 15, 2006;
133(10):
2041 - 2051.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. H. Yilmaz, M. J. Kiel, and S. J. Morrison
SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity
Blood,
February 1, 2006;
107(3):
924 - 930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, M. J. Chen, T. Stacy, and N. A. Speck
Runx1 function in hematopoiesis is required in cells that express Tek
Blood,
January 1, 2006;
107(1):
106 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, F. Yates, O. Naveiras, P. Ernst, and G. Q. Daley
Embryonic stem cell-derived hematopoietic stem cells
PNAS,
December 27, 2005;
102(52):
19081 - 19086.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Matsubara, A. Iwama, S. Yamazaki, C. Furuta, R. Hirasawa, Y. Morita, M. Osawa, T. Motohashi, K. Eto, H. Ema, et al.
Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development
J. Exp. Med.,
December 5, 2005;
202(11):
1483 - 1492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-F. Lin, D. Traver, H. Zhu, K. Dooley, B. H. Paw, L. I. Zon, and R. I. Handin
Analysis of thrombocyte development in CD41-GFP transgenic zebrafish
Blood,
December 1, 2005;
106(12):
3803 - 3810.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
T. M. Schlaeger, H. K. A. Mikkola, C. Gekas, H. B. Helgadottir, and S. H. Orkin
Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development
Blood,
May 15, 2005;
105(10):
3871 - 3874.
[Abstract]
[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]
|
|
|
|
|
|
|
J. R. Gothert, S. E. Gustin, M. A. Hall, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley
In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis
Blood,
April 1, 2005;
105(7):
2724 - 2732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Vodyanik, J. A. Bork, J. A. Thomson, and I. I. Slukvin
Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential
Blood,
January 15, 2005;
105(2):
617 - 626.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Y. Bertrand, S. Giroux, R. Golub, M. Klaine, A. Jalil, L. Boucontet, I. Godin, and A. Cumano
Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin
PNAS,
January 4, 2005;
102(1):
134 - 139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. I. Baumann, A. S. Bailey, W. Li, M. J. Ferkowicz, M. C. Yoder, and W. H. Fleming
PECAM-1 is expressed on hematopoietic stem cells throughout ontogeny and identifies a population of erythroid progenitors
Blood,
August 15, 2004;
104(4):
1010 - 1016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Burt, L. Verda, D.-A. Kim, Y. Oyama, K. Luo, and C. Link
Embryonic Stem Cells As an Alternate Marrow Donor Source: Engraftment without Graft-Versus-Host Disease
J. Exp. Med.,
April 5, 2004;
199(7):
895 - 904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Li, S. A. Johnson, W. C. Shelley, M. Ferkowicz, P. Morrison, Y. Li, and M. C. Yoder
Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro
Blood,
December 15, 2003;
102(13):
4345 - 4353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Sugiyama, M. Ogawa, I. Hirose, T. Jaffredo, K.-i. Arai, and K. Tsuji
Erythropoiesis from acetyl LDL incorporating endothelial cells at the preliver stage
Blood,
June 15, 2003;
101(12):
4733 - 4738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
