Abstract
BackgroundBoth human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse.ResultsTo assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human.ConclusionsOur findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.
Highlights
Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Klf4 and c-Myc (Sox2), Klf4, and c-Myc (OSKM) transcription factors
By expressing the transcription factors Oct4, Sox2, Klf4 and c-Myc, differentiated cells can be reprogrammed into induced pluripotent stem cells that have the ability to differentiate into any type of cell [1, 2]. iPSC technology holds great promise in regenerative medicine and for the modeling of diseases in a culture dish [3, 4]
General features of OSKM binding events in early human and mouse reprogramming In this study, we compare the binding of OSKM peaks in mouse and human at 48 h post transfection
Summary
Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct, Sox, Klf, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. By expressing the transcription factors Oct, Sox, Klf and c-Myc (abbreviated as OSKM), differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) that have the ability to differentiate into any type of cell [1, 2]. By investigating OSKM binding at 48 h of reprogramming, previous studies have begun to elucidate the patterns and regulatory roles of OSKM in early reprogramming in the human and mouse systems [8,9,10]. Koche et al demonstrated that within the first few days of iPS
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