Spyrou James, Gardner David K, Harvey Alexandra J
School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Stem Cells Int. 2019 May 5;2019:7360121. doi: 10.1155/2019/7360121. eCollection 2019.
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.
重编程为多能性涉及代谢和表观基因组的剧烈重组。然而，诱导多能干细胞（iPSC）保留了来自其起源体细胞的转录记忆、表观遗传记忆和代谢记忆，并获得了与其他多能细胞或亲代细胞不同的异常特征，这反映了重编程不完全。作为微环境与表观基因组调控之间的关键联系，营养物质的可用性可能在iPSC保留体细胞记忆方面发挥重要作用。值得注意的是，相对营养物质可用性会影响iPSC的重编程效率、表观遗传调控和细胞命运，并差异地改变它们对生理刺激的反应能力。代谢物在重编程过程中的重要性对于进一步阐明iPSC如何保留体细胞特征以及优化培养条件以产生具有生理表型的iPSC以确保其在基础研究和临床应用中的可靠使用至关重要。本综述旨在整合关于iPSC重编程、记忆保留和代谢的研究，并确定当前知识有限的领域。
