Immature hematopoietic stem cells undergo maturation in the fetal liver.
Hematopoietic stem cells (HSCs), which are defined by their capacity to reconstitute adult conventional mice, are first found in the dorsal aorta after 10.5 days post coitus (dpc) and in the fetal liver at 11 dpc. However, lympho-myeloid hematopoietic progenitors are detected in the dorsal aorta from 9 dpc, raising the issue of their role in establishing adult hematopoiesis. Here, we show that these progenitors are endowed with long-term reconstitution capacity, but only engraft natural killer (NK)-deficient Rag2γc(-/-) mice. This novel population, called here immature HSCs, evolves in culture with thrombopoietin and stromal cells, into HSCs, defined by acquisition of CD45 and MHC-1 expression and by the capacity to reconstitute NK-competent mice. This evolution occurs during ontogeny, as early colonization of fetal liver by immature HSCs precedes that of HSCs. Moreover, organ culture experiments show that immature HSCs acquire, in this environment, the features of HSCs.
Unite de Lymphopoièse, INSERM U668, Immunology Department, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Aurelie
A
Kieusseian
Philippe
P
Brunet de la Grange
Odile
O
Burlen-Defranoux
Isabelle
I
Godin
Ana
A
Cumano
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse