Journal
CELL
Volume 159, Issue 5, Pages 1070-1085Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.10.031
Keywords
-
Categories
Funding
- Spanish Ministry of Science and Innovation [BIO2011-23400, CSD2007-00002]
- Fundacion Seneca, Agencia Regional de Ciencia y Tecnologia de la Region de Murcia [04538/GERM/06]
- NIH [K01-DK087814-01A1, R01-DK074482]
- CIRM New Faculty Award [RN1-00575-1]
- AHA Innovative Science Award [12PILT12860010]
Ask authors/readers for more resources
Hematopoietic stemcells (HSCs) underlie the production of blood and immune cells for the lifetime of an organism. In vertebrate embryos, HSCs arise from the unique transdifferentiation of hemogenic endothelium comprising the floor of the dorsal aorta during a brief developmental window. To date, this process has not been replicated in vitro from pluripotent precursors, partly because the full complement of required signaling inputs remains to be determined. Here, we show that TNFR2 via TNF alpha activates the Notch and NF-kappa B signaling pathways to establish HSC fate, indicating a requirement for inflammatory signaling in HSC generation. We determine that primitive neutrophils are the major source of TNF alpha, assigning a role for transient innate immune cells in establishing the HSC program. These results demonstrate that proinflammatory signaling, in the absence of infection, is utilized by the developing embryo to generate the lineal precursors of the adult hematopoietic system.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available