Ex vivo reprogramming of human hematopoietic stem cells is accompanied by increased transcripts of genes regulating metabolic integrity.

Autor: Papa L; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Martin TC; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Djedaini M; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Zangui M; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Ozbek U; Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Parsons R; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Hoffman R; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: ronald.hoffman@mssm.edu., Schaniel C; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY; Mount Sinai Institute for System Biomedicine, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: christoph.schaniel@mssm.edu.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2023 Jun; Vol. 122, pp. 41-54. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1016/j.exphem.2023.03.006
Abstrakt: The regenerative potential of human hematopoietic stem cells (HSCs) is functionally defined by their ability to provide life-long blood cell production and to repopulate myeloablated allogeneic transplant recipients. The expansion of HSC numbers is dependent not only on HSC divisions but also on a coordinated adaptation of HSCs to metabolic stress. These variables are especially critical during the ex vivo culture of HSCs with cytokine combinations, which frequently results in HSC exhaustion. We have previously reported that human CD34 + hematopoietic stem and progenitor cells (HSPCs) can be efficiently reprogrammed ex vivo and that the number of phenotypic HSCs with long-term repopulation capacity is expanded in the presence of a combination of cytokines and an epigenetic modifier. Here, we present evidence that ex vivo HSC reprogramming and maintenance is accompanied by increased transcripts of genes regulating metabolic integrity, including SIRT1 and SIRT3.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2023 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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