Metabolic maturation of differentiating cardiosphere-derived cells.

Autor:	Pakzad KK; Department of Physiology, Anatomy & Genetics, University of Oxford, UK., Tan JJ; Department of Physiology, Anatomy & Genetics, University of Oxford, UK; Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia., Anderson S; Department of Physiology, Anatomy & Genetics, University of Oxford, UK., Board M; Department of Physiology, Anatomy & Genetics, University of Oxford, UK., Clarke K; Department of Physiology, Anatomy & Genetics, University of Oxford, UK., Carr CA; Department of Physiology, Anatomy & Genetics, University of Oxford, UK. Electronic address: Carolyn.carr@dpag.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2021 Jul; Vol. 54, pp. 102422. Date of Electronic Publication: 2021 Jun 05.
DOI:	10.1016/j.scr.2021.102422
Abstrakt:	Cardiosphere-derived cells (CDCs) can be expanded in vitro and induced to differentiate along the cardiac lineage. To recapitulate the phenotype of an adult cardiomyocyte, differentiating progenitors need to upregulate mitochondrial glucose and fatty acid oxidation. Here we cultured and differentiated CDCs using protocols aimed to maintain stemness or to promote differentiation, including triggering fatty acid oxidation using an agonist of peroxisome proliferator-activated receptor alpha (PPARα). Metabolic changes were characterised in undifferentiated CDCs and during differentiation towards a cardiac phenotype. CDCs from rat atria were expanded on fibronectin or collagen IV via cardiosphere formation. Differentiation was assessed using flow cytometry and qPCR and substrate metabolism was quantified using radiolabelled substrates. Collagen IV promoted proliferation of CDCs whereas fibronectin primed cells for differentiation towards a cardiac phenotype. In both populations, treatment with 5-Azacytidine induced a switch towards oxidative metabolism, as shown by changes in gene expression, decreased glycolytic flux and increased oxidation of glucose and palmitate. Addition of a PPARα agonist during differentiation increased both glucose and fatty acid oxidation and expression of cardiac genes. We conclude that oxidative metabolism and cell differentiation act in partnership with increases in one driving an increase in the other. (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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