Abstract
In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be the sole location for intraembryonic emergence of hematopoietic stem cells (HSCs). Here we report that, in parallel to the AGM region, the E10.5-E11.5 mouse head harbors bona fide HSCs, as defined by long-term, high-level, multilineage reconstitution and self-renewal capacity in adult recipients, before HSCs enter the circulation. The presence of hemogenesis in the midgestation head is indicated by the appearance of intravascular cluster cells and the blood-forming capacity of a sorted endothelial cell population. In addition, lineage tracing via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of head endothelium. Most importantly, a spatially restricted lineage labeling system reveals the physiological contribution of cerebrovascular endothelium to postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse embryonic head is a previously unappreciated site for HSC emergence within the developing embryo.
Original language | English |
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Pages (from-to) | 663-75 |
Number of pages | 13 |
Journal | Cell Stem Cell |
Volume | 11 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2 Nov 2012 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Antigens, CD
- Aorta
- Cadherins
- Cell Differentiation
- Cell Lineage
- Embryo, Mammalian
- Endothelium, Vascular
- Gonads
- Head
- Hematopoietic Stem Cells
- Mesonephros
- Mice
- Transgenes