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Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells.
Szade, Krzysztof; Zukowska, Monika; Szade, Agata; Nowak, Witold; Skulimowska, Izabella; Ciesla, Maciej; Bukowska-Strakova, Karolina; Gulati, Gunsagar Singh; Kachamakova-Trojanowska, Neli; Kusienicka, Anna; Einwallner, Elisa; Kijowski, Jacek; Czauderna, Szymon; Esterbauer, Harald; Benes, Vladimir; L Weissman, Irving; Dulak, Jozef; Jozkowicz, Alicja.
Afiliação
  • Szade K; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Zukowska M; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Szade A; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Nowak W; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Skulimowska I; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Ciesla M; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Bukowska-Strakova K; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Gulati GS; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Kachamakova-Trojanowska N; Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
  • Kusienicka A; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Einwallner E; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Kijowski J; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
  • Czauderna S; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Esterbauer H; Department of Laboratory Medicine, Center of Translational Research, Medical University of Vienna, Vienna, Austria.
  • Benes V; Department of Transplantation, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
  • L Weissman I; Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
  • Dulak J; Department of Laboratory Medicine, Center of Translational Research, Medical University of Vienna, Vienna, Austria.
  • Jozkowicz A; Genomics Core Facility, EMBL Heidelberg, Heidelberg, Germany.
EMBO Rep ; 21(2): e47895, 2020 02 05.
Article em En | MEDLINE | ID: mdl-31885181
ABSTRACT
While intrinsic changes in aging hematopoietic stem cells (HSCs) are well characterized, it remains unclear how extrinsic factors affect HSC aging. Here, we demonstrate that cells in the niche-endothelial cells (ECs) and CXCL12-abundant reticular cells (CARs)-highly express the heme-degrading enzyme, heme oxygenase 1 (HO-1), but then decrease its expression with age. HO-1-deficient animals (HO-1-/- ) have altered numbers of ECs and CARs that produce less hematopoietic factors. HSCs co-cultured in vitro with HO-1-/- mesenchymal stromal cells expand, but have altered kinetic of growth and differentiation of derived colonies. HSCs from young HO-1-/- animals have reduced quiescence and regenerative potential. Young HO-1-/- HSCs exhibit features of premature exhaustion on the transcriptional and functional level. HO-1+/+ HSCs transplanted into HO-1-/- recipients exhaust their regenerative potential early and do not reconstitute secondary recipients. In turn, transplantation of HO-1-/- HSCs to the HO-1+/+ recipients recovers the regenerative potential of HO-1-/- HSCs and reverses their transcriptional alterations. Thus, HSC-extrinsic activity of HO-1 prevents HSCs from premature exhaustion and may restore the function of aged HSCs.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Heme Oxigenase-1 / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Heme Oxigenase-1 / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article