Identification of chemicals that facilitate induced pluripotent stem cell generation through upregulating E-cadherin expression

On Jun 2, 2010, Stem Cells online published a research article entitled "E-cadherin-Mediated Cell-Cell Contact is Critical for Induced Pluripotent Stem Cell Generation" from Prof. Pei Gang’s group in Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), CAS.

 

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 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.

 

Through screening a chemical library, Chen and Yuan et al. found that two chemicals reported to upregulate E-cadherin considerably increase the reprogramming efficiency. Further study of the process indicated that E-cadherin is upregulated during reprogramming and the established iPS cells possess E-cadherin-mediated cell-cell contact, morphologically indistinguishable from ES cells. Their experiments also demonstrate that overexpression of E-cadherin significantly enhances reprogramming efficiency, whereas knockdown of endogenous E-cadherin by shRNA reduces the efficiency. Consistently, abrogation of cell-cell contact by the inhibitory peptide or the neutralizing antibody against the extracellular domain of E-cadherin compromises iPS cell generation. Further mechanistic study reveals that adhesive binding activity of E-cadherin is required. As commented by the reviewers, Pei and his colleagues not only highlight the critical role of E-cadherin-mediated cell-cell contact in reprogramming, but also suggest new routes for more efficient iPS cell generation.

 

This research was supported by grants from the Ministry of Science and Technology, National Natural Science Foundation of China, and Chinese Academy of Sciences.