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

来源组织对重编程的影响 来源组织已被证明会影响诱导多能干细胞（iPSC）的重编程效率和行为。例如，黑素细胞比成纤维细胞更容易重编程，造血干细胞和祖细胞比终末分化的B和T细胞更有效地产生IPSC。 此外，最近来自严格定义的小鼠重编程模型的研究表明，在早期传代的IPSC中可以观察到基因表达、分化潜力和DNA甲基化模式的细胞类型的来源特异性差异，这导致了一种假设，即过去命运的表观遗传记忆在iPSC中持续存在，尽管它似乎是短暂的并且在连续传代后变得减轻。 尽管这些差异的机制基础尚未得到很好的理解，但越来越清楚的是，来源组织表达的转录因子、增殖特性和表观遗传差异有望在所得iPSC的重编程效率和发育潜力中发挥关键的来源组织特异性差异。

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.