Abstract:
Nuclear reprogramming is a crucial event for many developmental processes and tissue repair. Although landmark studies have shown that reprogramming can be induced by external biochemical agents, the function of mechanical cue in reprogramming has not been well described. In a recent work, we showed nuclear reprogramming can be triggered by laterally confined growth of fibroblasts on fibronectin covered micropatterned with high efficiency without the introduction of any external biochemical reagents. In this study we show that human fibroblasts gain stemness properties following 8-10 days of laterally confined growth. This has been corroborated by the expression of pluripotency markers and alkaline phosphatase assays. Importantly, we describe the temporal changes of the structural components during reprogramming. Here we provide compelling evidence to show that actin cytoskeleton has a critical role in the maintenance of the geometrical features of spheroids. In addition to this, we also show the global change in H3K9Ac levels. Our finding throws light upon the unknown mechanism of mechanical cue induced somatic cell reprogramming. Taken together, this study highlights interesting facets of the spatio-temporal dynamics of structural components and epigenetic landscape during nuclear reprogramming by laterally confined growth.
