Human induced pluripotent stem cells derived under feeder-free conditions display unique cell cycle and DNA replication gene profiles

在无饲养条件下衍生的人类诱导多能干细胞表现出独特的细胞周期和 DNA 复制基因谱

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作者:Henry C Y Chung, Ruby C Y Lin, Grant J Logan, Ian E Alexander, Perminder S Sachdev, Kuldip S Sidhu

Abstract

Use of animal feeder layers and serum containing media in the derivation and propagation of induced pluripotent stem cells (iPSCs) can hinder clinical translation, because of the presence of xeno-material/pathogens. A defined and standardized system would be ideal for generating a homogenous population of iPSCs, which closely resembles human embryonic stem cells (hESCs). This article presents a novel and extensive comparison between in-house produced iPSCs and hESCs under "feeder" and "feeder-free" conditions, using transcriptomic genome-wide microarray analysis. We generated a list of pluripotency-associated and bivalent domain-containing genes by meta-analysis to measure qualitatively the degree of reprogramming in feeder-free derived iPSCs, in which both profiles displayed similar levels of gene expression as in hESCs. Gene ontology analysis showed that feeder-free iPSCs have enriched terms belonging to DNA repair/replication and cell cycle, which are signature to pluripotent cells. Transcriptomic data combined with directed differentiation assays, indicated that variability among iPSC lines is minimized when using a feeder-free cultural system, which may serve as a platform for further developing regenerative medicine compliant human iPSCs.

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