E-cadherin-Mediated Cell-Cell Contact is Critical for Induced Pluripotent Stem Cell Generation

Induced pluripotent stem (iPS) cells can be generated by direct reprogramming of somatic cells through ectopic expression of defined transcription factors, classically a combination of four factors, Oct3/4, Sox2, c-Myc and Klf4. iPS cells represent an intriguing new source for patient specific pluripotent stem cells; therefore many efforts have been taken to make iPS cells more amenable for therapeutic application. In order to improve the iPS generation efficiency and avoid the oncogenic effect of viral vectors, reduced number of factors as well as small molecules was used to optimize the iPS generation technology. However, the reprogramming process is still highly inefficient. A better understanding of the mechanisms underlying the reprogramming process might help us identify other pathways or cooperative factors to improve the reprogramming efficiency.

 

In this research we report that two small molecules with reported activity to upregulate E-cadherin expression can increase the reprogramming efficiency. We find that E-cadherin expression is upregulated in the early stage of reprogramming, and the cell-cell contact in iPS cells is mainly mediated by E-cadherin. Enhanced iPS cell generation can be achieved by overexpression of E-cadherin, whereas knockdown of endogenous E-cadherin or abrogation of cell-cell contact by E-cadherin inhibition results in reduced reprogramming efficiency. Further mechanistic study demonstrates that the adhesive binding activity is essential for the reprogramming process.

 

This research was supported by grants from the Ministry of Science and Technology, National Natural Science Foundation of China, Shanghai Municipal Commission for Science and Technology, Natural Science Foundation of Shanghai.