Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors

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Item Type:	Article
Title:	Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors
Creators Name:	Haas, S., Hansson, J., Klimmeck, D., Loeffler, D., Velten, L., Uckelmann, H., Wurzer, S., Prendergast, Á.M., Schnell, A., Hexel, K., Santarella-Mellwig, R., Blaszkiewicz, S., Kuck, A., Geiger, H., Milsom, M.D., Steinmetz, L.M., Schroeder, T., Trumpp, A., Krijgsveld, J. and Essers, M.A.G.
Abstract:	Infections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults. During homeostasis, SL-MkPs are maintained in a primed but quiescent state, thus contributing little to steady-state megakaryopoiesis. Even though lineage-specific megakaryocyte transcripts are expressed, protein synthesis is suppressed. In response to acute inflammation, SL-MkPs become activated, resulting in megakaryocyte protein production from pre-existing transcripts and a maturation of SL-MkPs and other megakaryocyte progenitors. This results in an efficient replenishment of platelets that are lost during inflammatory insult. Thus, our study reveals an emergency machinery that counteracts life-threatening platelet depletions during acute inflammation.
Keywords:	Blood Platelets, Cell Lineage, Cell Proliferation, Hematopoietic Stem Cells, Inflammation, Megakaryocyte Progenitor Cells, Thrombopoiesis, Animals, Mice
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Cell Press
Volume:	17
Number:	4
Page Range:	422-34
Date:	1 October 2015
Official Publication:	https://doi.org/10.1016/j.stem.2015.07.007
PubMed:	View item in PubMed

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