Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo

Blood. 2003 Jan 15;101(2):508-16. doi: 10.1182/blood-2002-06-1699. Epub 2002 Sep 19.


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 CD45(-)CD41(+) 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.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Culture Techniques
  • DNA-Binding Proteins / genetics
  • Embryo, Mammalian / physiology*
  • Endothelium / cytology
  • Endothelium / embryology
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology
  • Immunophenotyping
  • Leukocyte Common Antigens / biosynthesis
  • Mice
  • Platelet Membrane Glycoprotein IIb / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Stem Cells / cytology
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors / genetics
  • Yolk Sac / cytology


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Platelet Membrane Glycoprotein IIb
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • Transcription Factors
  • Leukocyte Common Antigens