Extraneous E-Cadherin Engages the Deterministic Process of Somatic Reprogramming through Modulating STAT3 and Erk1/2 Activity

Although several modes of reprogramming have been reported in different cell types during iPSC induction, the molecular mechanism regarding the selection of different modes of action is still mostly unknown. The present study examined the molecular events that participate in the selection of such processes at the onset of somatic reprogramming. The activity of STAT3 versus that of Erk1/2 reversibly determines the reprogramming mode entered; a lower activity ratio favors the deterministic process and vice versa. Additionally, extraneous E-cadherin facilitates the early events of somatic reprogramming, potentially by stabilizing the LIF/gp130 and EGFR/ErbB2 complexes to promote entry into the deterministic process. Our current findings demonstrated that manipulating the pSTAT3/pErk1/2 activity ratio in the surrounding milieu can drive different modes of action toward either the deterministic or the stochastic process in the context of OSKM-mediated somatic reprogramming.

Automated summary

This study investigated the molecular events involved in the selection of reprogramming modes during somatic reprogramming, revealing that the activity ratio of STAT3 and Erk1/2 determines whether the process is deterministic or stochastic. Additionally, extrinsic E-cadherin was found to facilitate early events of somatic reprogramming by stabilizing certain complexes. Manipulating the pSTAT3/pErk1/2 activity ratio in the microenvironment can drive different modes of action in OSKM-mediated somatic reprogramming.