Abstract
Somatic cell nuclear transfer (SCNT) or the forced expression of transcription factors can be used to generate autologous pluripotent stem cells (PSCs). Although transcriptomic and epigenomic comparisons of isogenic human NT-embryonic stem cells (NT-ESCs) and induced PSCs (iPSCs) in the undifferentiated state have been reported, their functional similarities and differentiation potentials have not been fully elucidated. Our study showed that NT-ESCs and iPSCs derived from the same donors generally displayed similar in vitro commitment capacity toward three germ layer lineages as well as proliferative activity and clonogenic capacity. However, the maturation capacity of NT-ESC-derived hematopoietic progenitors was significantly greater than the corresponding capacity of isogenic iPSC-derived progenitors. Additionally, donor-dependent variations in hematopoietic specification and commitment capacity were observed. Transcriptome and methylome analyses in undifferentiated NT-ESCs and iPSCs revealed a set of genes that may influence variations in hematopoietic commitment and maturation between PSC lines derived using different reprogramming methods. Here, we suggest that genetically identical iPSCs and NT-ESCs could be functionally unequal due to differential transcription and methylation levels acquired during reprogramming. Our proof-of-concept study indicates that reprogramming mechanisms and genetic background could contribute to diverse functionalities between PSCs.
Highlights
Introduction Human pluripotentESCs, which are successfully derived by isolating an inner cell mass from a viable blastocyst, are allogeneic[1]
The unsupervised hierarchical clustering of the isogenic induced PSCs (iPSCs) and NT-embryonic stem cells (NT-ESCs) pairs clearly indicated that the mRNA landscapes of the undifferentiated pluripotent cells were primarily donordependent (Supplementary Fig. 5c)
We found that dissociated iPSCs and NT-ESCs both propagated as undifferentiated cultures that were morphologically identical to the original cultures and that exhibited a similar clonogenic capacity (Fig. 1d, e)
Summary
Introduction Human pluripotentESCs, which are successfully derived by isolating an inner cell mass from a viable blastocyst, are allogeneic[1]. To overcome the issue of allogeneity, two innovative reprogramming approaches for converting somatic cells into PSCs were evaluated. We and two other research groups independently reported the establishment of diploid pluripotent ESCs by transferring the nucleus of fetal and adult fibroblasts into enucleated oocytes[4,5,6]. These two reprogramming methods yield autologous PSCs, which could be suitable for the development of patient-specific cell therapies that do not cause immune rejection[7]. Determining whether iPSCs and NTESCs are genetically safe and functionally competent is critical prior to their use in personalized regenerative medicine
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