Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2
View/ Open
Author
Mohammad, Khalid S.
Singh, Pratibha
Hoggatt, Amber F.
Chitteti, Brahmananda Reddy
Speth, Jennifer M.
Hu, Peirong
Poteat, Bradley A.
Stilger, Kayla N.
Ferraro, Francesca
Wong, Frankie K.
Farag, Sherif S.
Czader, Magdalena
Milne, Ginger L.
Breyer, Richard M.
Serezani, Carlos H.
Guise, Theresa
Srour, Edward F.
Pelus, Louis M.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nature11929Metadata
Show full item recordCitation
Hoggatt, J., K. S. Mohammad, P. Singh, A. F. Hoggatt, B. R. Chitteti, J. M. Speth, P. Hu, et al. 2013. “Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2.” Nature 495 (7441): 365-369. doi:10.1038/nature11929. http://dx.doi.org/10.1038/nature11929.Abstract
SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606692/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11876987
Collections
- FAS Scholarly Articles [18292]
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)