Haploinsufficiency of AML1 affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo.
The AML1:CBFbeta transcription factor complex is essential for definitive hematopoiesis. Null mutations in mouse AML1 result in midgestational lethality with a complete lack of fetal liver hematopoiesis. While the cell autonomous nature and expression pattern of AML1 suggest an intrinsic role for this transcription factor in the developing hematopoietic system, no direct link to a functional cell type has been made. Here, we examine the consequences of AML1 loss in hematopoietic stem cells (HSC) of the mouse embryo. We demonstrate an absolute requirement for AML1 in functional HSCs. Moreover, haploinsufficiency results in a dramatic change in the temporal and spatial distribution of HSCs, leading to their early appearance in the normal position in the aorta-gonad-mesonephros region and also in the yolk sac.
Cai
Z
Z
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
de Bruijn
M
M
Ma
X
X
Dortland
B
B
Luteijn
T
T
Downing
R J
RJ
Dzierzak
E
E
D000818:Animals; D001011:Aorta / Q000196:embryology / Q000637:transplantation; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003114:Colony-Forming Units Assay; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000502:physiology; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005260:Female; D005865:Gestational Age; D006066:Gonads / Q000196:embryology / Q000637:transplantation; D006239:Haplotypes / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology*; D008297:Male; D008650:Mesonephros / Q000196:embryology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000008:administration & dosage / Q000235:genetics* / Q000502:physiology; D015017:Yolk Sac / Q000196:embryology / Q000637:transplantation
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors