期刊
DEVELOPMENT
卷 139, 期 19, 页码 3521-3530出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.079210
关键词
MHC class I; Fetal liver; Hematopoietic reconstitution; Hematopoietic stem cells
资金
- INSERM
- FP6 Eurostemcell Consortium
- Agence National de la Recherche
- La Ligue Contre le Cancer
- Association pour la Recherche sur le Cancer [4878]
- La Fondation pour la Recherche Medicale
- Agence Nationale de la Recherche
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 Rag2 gamma c(-/-) 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.
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