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Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation.
Heil, Joschka; Olsavszky, Victor; Busch, Katrin; Klapproth, Kay; de la Torre, Carolina; Sticht, Carsten; Sandorski, Kajetan; Hoffmann, Johannes; Schönhaber, Hiltrud; Zierow, Johanna; Winkler, Manuel; Schmid, Christian David; Staniczek, Theresa; Daniels, Deborah E; Frayne, Jan; Metzgeroth, Georgia; Nowak, Daniel; Schneider, Sven; Neumaier, Michael; Weyer, Vanessa; Groden, Christoph; Gröne, Hermann-Josef; Richter, Karsten; Mogler, Carolin; Taketo, Makoto Mark; Schledzewski, Kai; Géraud, Cyrill; Goerdt, Sergij; Koch, Philipp-Sebastian.
Afiliación
  • Heil J; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Olsavszky V; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Busch K; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany. victor.olsavszky@umm.de.
  • Klapproth K; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. victor.olsavszky@umm.de.
  • de la Torre C; Division of Cellular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Sticht C; Division of Cellular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Sandorski K; Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Hoffmann J; Core Facility Platform Mannheim (CFPM), NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Schönhaber H; Core Facility Platform Mannheim (CFPM), NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Zierow J; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Winkler M; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Schmid CD; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Staniczek T; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Daniels DE; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Frayne J; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Metzgeroth G; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Nowak D; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Schneider S; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Neumaier M; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Weyer V; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Groden C; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany.
  • Gröne HJ; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Richter K; School of Biochemistry, University of Bristol, Bristol, UK.
  • Mogler C; School of Biochemistry, University of Bristol, Bristol, UK.
  • Taketo MM; Department for Hematology and Oncology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Schledzewski K; Department for Hematology and Oncology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Géraud C; Institute for Clinical Chemistry, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Goerdt S; Institute for Clinical Chemistry, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Koch PS; Department of Neuroradiology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Nat Commun ; 12(1): 6963, 2021 11 29.
Article en En | MEDLINE | ID: mdl-34845225
ABSTRACT
Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized ß-catenin in BM-SEC (Ctnnb1OE-SEC) generated by using a BM-SEC-restricted Cre mouse line (Stab2-iCreF3) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII-PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1OE-SEC hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1OE-SEC BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Médula Ósea / Endotelio Vascular / Moléculas de Adhesión Celular Neuronal / Eritroblastos / Eritropoyesis / Beta Catenina / Anemia Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Médula Ósea / Endotelio Vascular / Moléculas de Adhesión Celular Neuronal / Eritroblastos / Eritropoyesis / Beta Catenina / Anemia Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania