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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Simon Haas
  • Jenny Hansson
  • Daniel Klimmeck
  • Dirk Loeffler
  • Lars Velten
  • Hannah Uckelmann
  • Stephan Wurzer
  • Áine M Prendergast
  • Alexandra Schnell
  • Klaus Hexel
  • Rachel Santarella-Mellwig
  • Sandra Blaszkiewicz
  • Andrea Kuck
  • Hartmut Geiger
  • Michael D Milsom
  • Lars M Steinmetz
  • Timm Schroeder
  • Andreas Trumpp
  • Jeroen Krijgsveld
  • Marieke A G Essers
Organisations
External organisations
  • European Molecular Biology Laboratory Heidelberg
Original languageEnglish
Pages (from-to)422-34
Number of pages13
JournalCell Stem Cell
Volume17
Issue number4
Publication statusPublished - 2015 Oct 1
Publication categoryResearch
Peer-reviewedYes