Helmholtz Gemeinschaft


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

Item Type:Article
Title:Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors
Creators Name:Haas, S. and Hansson, J. and Klimmeck, D. and Loeffler, D. and Velten, L. and Uckelmann, H. and Wurzer, S. and Prendergast, Á.M. and Schnell, A. and Hexel, K. and Santarella-Mellwig, R. and Blaszkiewicz, S. and Kuck, A. and Geiger, H. and Milsom, M.D. and Steinmetz, L.M. and Schroeder, T. and Trumpp, A. and 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
Publisher:Cell Press
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

Repository Staff Only: item control page

Open Access
MDC Library