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Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration.
Engelhard, Sophia; Estruch, Montserrat; Qin, Shuyu; Engelhard, Christoph A; Rodriguez-Gonzalez, Francisco G; Drilsvik, Martine; Martin-Gonzalez, Javier; Lu, Jeng-Wei; Bryder, David; Nerlov, Claus; Weischenfeldt, Joachim; Reckzeh, Kristian; Theilgaard-Mönch, Kim.
Afiliación
  • Engelhard S; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copen
  • Estruch M; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Qin S; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Engelhard CA; Center for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department for Biochemistry and Molecular Biology (BMB), University of Southern Denmark, Odense, Denmark.
  • Rodriguez-Gonzalez FG; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Drilsvik M; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Martin-Gonzalez J; Core Facility for Transgenic Mice, Department of Experimental Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Lu JW; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Bryder D; Division of Molecular Hematology, Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Nerlov C; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK.
  • Weischenfeldt J; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Reckzeh K; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Symphogen, Ballerup, Denmark. Electronic address: kristian.reckzeh@gemail.com.
  • Theilgaard-Mönch K; Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copen
Cell Rep ; 43(7): 114475, 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-38996072
ABSTRACT
Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48-LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN- LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN- LT-HSCs. Emcn-/- and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn-/- LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn-/- or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Linaje de la Célula / Hematopoyesis Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Linaje de la Célula / Hematopoyesis Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos