title: Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors.
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.
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Simon
authors: S
authors: Haas
authors: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
authors: Jenny
authors: J
authors: Hansson
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Daniel
authors: D
authors: Klimmeck
authors: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, 4058 Basel, Switzerland.
authors: Dirk
authors: D
authors: Loeffler
authors: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
authors: Lars
authors: L
authors: Velten
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Hannah
authors: H
authors: Uckelmann
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Stephan
authors: S
authors: Wurzer
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Áine M
authors: ÁM
authors: Prendergast
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Alexandra
authors: A
authors: Schnell
authors: Core Facility Flow Cytometry, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Klaus
authors: K
authors: Hexel
authors: European Molecular Biology Laboratory (EMBL), Electron Microscopy Core Facility, 69117 Heidelberg, Germany.
authors: Rachel
authors: R
authors: Santarella-Mellwig
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Sandra
authors: S
authors: Blaszkiewicz
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Andrea
authors: A
authors: Kuck
authors: Institute for Molecular Medicine, Ulm University, 89081 Ulm, Germany; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA.
authors: Hartmut
authors: H
authors: Geiger
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Experimental Hematology Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Michael D
authors: MD
authors: Milsom
authors: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany; Stanford Genome Technology Center, Palo Alto, CA 94304, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Lars M
authors: LM
authors: Steinmetz
authors: Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, 4058 Basel, Switzerland.
authors: Timm
authors: T
authors: Schroeder
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors: Andreas
authors: A
authors: Trumpp
authors: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
authors: Jeroen
authors: J
authors: Krijgsveld
authors: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Hematopoietic Stem Cells and Stress Group, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany. Electronic address: m.essers@dkfz.de.
authors: Marieke A G
authors: MA
authors: Essers
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000473:pathology* / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D007249:Inflammation / Q000473:pathology*; D055016:Megakaryocyte Progenitor Cells / Q000473:pathology* / Q000502:physiology; D051379:Mice; D034061:Thrombopoiesis