Fig. 7.

Schematic model for the enhanced reprogramming of human somatic cells by LIN28, NANOG and iDOT1L. Proposed model: the enhanced human somatic cell reprogramming by NANOG and LIN28 involves their synergy in activation of LIN41, which is a target of LIN28/Let-7 pathway. LIN41 can replace LIN28 to synergize with NANOG, achieving the same amplification of reprogramming efficiency as the NANOG and LIN28 combination. This synergy can be further enhanced with the inhibition of H3K79 methyltransferase DOT1L. The strong stimulation of MET and activation of the canonical WNT signaling pathway contribute to the massive colony formation in the optimized reprogramming system. For the WNT pathway, despite its positive role in promoting colony formation, hyperactivation of WNT triggers the differentiation of the emerging presumptive colonies. Hence, inhibition of the WNT pathway by IWR1 at late stage of reprogramming can promote the maturation of the emerging colony, without compromising the induced iPSC colony numbers. A thicker line within the graph indicates a stronger stimulation or inhibition compared with a thinner line toward the same biological effect.