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Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors

Haas, Simon; Hansson, Jenny LU ; Klimmeck, Daniel; Loeffler, Dirk; Velten, Lars; Uckelmann, Hannah; Wurzer, Stephan; Prendergast, Áine M; Schnell, Alexandra and Hexel, Klaus, et al. (2015) In Cell Stem Cell 17(4). p.34-422
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... (More)

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.

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published
in
Cell Stem Cell
volume
17
issue
4
pages
13 pages
publisher
Cell Press
external identifiers
  • Scopus:84952628356
ISSN
1934-5909
DOI
10.1016/j.stem.2015.07.007
language
English
LU publication?
no
id
006a82ee-ca5c-4f5e-864a-8b7bb4df2607
date added to LUP
2016-04-19 10:14:30
date last changed
2016-12-04 04:50:35
@misc{006a82ee-ca5c-4f5e-864a-8b7bb4df2607,
  abstract     = {<p>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.</p>},
  author       = {Haas, Simon and Hansson, Jenny and Klimmeck, Daniel and Loeffler, Dirk and Velten, Lars and Uckelmann, Hannah and Wurzer, Stephan and Prendergast, Áine M and Schnell, Alexandra and Hexel, Klaus and Santarella-Mellwig, Rachel and Blaszkiewicz, Sandra and Kuck, Andrea and Geiger, Hartmut and Milsom, Michael D and Steinmetz, Lars M and Schroeder, Timm and Trumpp, Andreas and Krijgsveld, Jeroen and Essers, Marieke A G},
  issn         = {1934-5909},
  language     = {eng},
  month        = {10},
  number       = {4},
  pages        = {34--422},
  publisher    = {ARRAY(0x8864898)},
  series       = {Cell Stem Cell},
  title        = {Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors},
  url          = {http://dx.doi.org/10.1016/j.stem.2015.07.007},
  volume       = {17},
  year         = {2015},
}