Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming

Reprogramming to pluripotency involves drastic restructuring of both metabolism and the epigenome. However, induced pluripotent stem cells (iPSC) retain transcriptional memory, epigenetic memory, and metabolic memory from their somatic cells of origin and acquire aberrant characteristics distinct fr...

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Main Authors: James Spyrou, David K. Gardner, Alexandra J. Harvey
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/7360121
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author James Spyrou
David K. Gardner
Alexandra J. Harvey
author_facet James Spyrou
David K. Gardner
Alexandra J. Harvey
author_sort James Spyrou
collection DOAJ
description Reprogramming to pluripotency involves drastic restructuring of both metabolism and the epigenome. However, induced pluripotent stem cells (iPSC) retain transcriptional memory, epigenetic memory, and metabolic memory from their somatic cells of origin and acquire aberrant characteristics distinct from either other pluripotent cells or parental cells, reflecting incomplete reprogramming. As a critical link between the microenvironment and regulation of the epigenome, nutrient availability likely plays a significant role in the retention of somatic cell memory by iPSC. Significantly, relative nutrient availability impacts iPSC reprogramming efficiency, epigenetic regulation and cell fate, and differentially alters their ability to respond to physiological stimuli. The significance of metabolites during the reprogramming process is central to further elucidating how iPSC retain somatic cell characteristics and optimising culture conditions to generate iPSC with physiological phenotypes to ensure their reliable use in basic research and clinical applications. This review serves to integrate studies on iPSC reprogramming, memory retention and metabolism, and identifies areas in which current knowledge is limited.
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spelling doaj-art-0ffc2e0bc8424c67aab1e40e588471422025-02-03T01:23:44ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/73601217360121Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell ReprogrammingJames Spyrou0David K. Gardner1Alexandra J. Harvey2School of BioSciences, The University of Melbourne, Parkville, VIC 3010, AustraliaSchool of BioSciences, The University of Melbourne, Parkville, VIC 3010, AustraliaSchool of BioSciences, The University of Melbourne, Parkville, VIC 3010, AustraliaReprogramming to pluripotency involves drastic restructuring of both metabolism and the epigenome. However, induced pluripotent stem cells (iPSC) retain transcriptional memory, epigenetic memory, and metabolic memory from their somatic cells of origin and acquire aberrant characteristics distinct from either other pluripotent cells or parental cells, reflecting incomplete reprogramming. As a critical link between the microenvironment and regulation of the epigenome, nutrient availability likely plays a significant role in the retention of somatic cell memory by iPSC. Significantly, relative nutrient availability impacts iPSC reprogramming efficiency, epigenetic regulation and cell fate, and differentially alters their ability to respond to physiological stimuli. The significance of metabolites during the reprogramming process is central to further elucidating how iPSC retain somatic cell characteristics and optimising culture conditions to generate iPSC with physiological phenotypes to ensure their reliable use in basic research and clinical applications. This review serves to integrate studies on iPSC reprogramming, memory retention and metabolism, and identifies areas in which current knowledge is limited.http://dx.doi.org/10.1155/2019/7360121
spellingShingle James Spyrou
David K. Gardner
Alexandra J. Harvey
Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
Stem Cells International
title Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
title_full Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
title_fullStr Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
title_full_unstemmed Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
title_short Metabolism Is a Key Regulator of Induced Pluripotent Stem Cell Reprogramming
title_sort metabolism is a key regulator of induced pluripotent stem cell reprogramming
url http://dx.doi.org/10.1155/2019/7360121
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