Project 2: Tissue-of-Origin Effects on Epigenome Remodeling During Reprogramming

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Tissue of origin effects on reprogramming Tissue of origin has been shown to influence the efficiency of reprogramming and the behavior of induced pluripotent stem cells (iPSCs). For example, melanocytes reprogram more readily than fibroblasts, and hematopoietic stem and progenitor cells give rise to IPSC much more efficiently than terminally differentiated B and T cells. Furthermore, recent studies from stringently defined mouse reprogramming models show that cell-type of origin-specific differences in gene expression, differentiation potential and DNA methylation patterns can be observed in eariy passage IPSCs, leading to a hypothesis that an epigenetic memory of the past fate persists in iPSCs, although it appears to be transient and becomes alleviated upon continuous passaging. Although the mechanistic basis of these differences is not well understood, it is becoming clear that tissue-of-origin-expressed transcription factors, proliferative properties and epigenetic differences are poised to play a pivotal tissue-of-origin specific differences in the efficiency of reprogramming and developmental potential of the resultant iPSCs.