Different tissues show variable susceptibility to reprogramming. Keratinocytes reprogram more readily than fibroblasts9, and iPSC from stomach or liver cells harbor fewer integrated proviruses than fibroblasts, suggesting they require lower levels of the reprogramming factors to achieve pluripotency10. When differentiated into neurospheres, iPSC from adult tail-tip fibroblasts retain more teratoma-forming cells than iPSC from embryonic fibroblasts, again indicating heterogeneity based on the tissue of origin11. Moreover, cells can exist in intermediate states of reprogramming that interconvert with continuous passage or treatment with chromatin-modifying agents1213. Although generic iPSC are highly similar to fESC, in practice iPSC generated from various tissues may harbor significant differences, both functional and molecular.
