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Publication : Retinoic acid promotes stem cell differentiation and embryonic development by transcriptionally activating CFTR.

First Author  Li X Year  2018
Journal  Biochim Biophys Acta Volume  1865
Issue  4 Pages  605-615
PubMed ID  29326073 Mgi Jnum  J:261853
Mgi Id  MGI:6158189 Doi  10.1016/j.bbamcr.2018.01.005
Citation  Li X, et al. (2018) Retinoic acid promotes stem cell differentiation and embryonic development by transcriptionally activating CFTR. Biochim Biophys Acta 1865(4):605-615
abstractText  Retinoic acid (RA) plays a pivotal role in many cellular processes; however, the signaling mechanisms mediating the effect of RA are not fully understood. Here, we show that RA transcriptionally upregulates cystic fibrosis transmembrane conductance regulator (Cftr) by promoting the direct binding of its receptor RARalpha to Cftr promoter in mouse spermatogonia and embryonic stem (ES) cells. The RA/CFTR pathway is involved in the differentiation of spermatogonia and organogenesis during the embryo development of Xenopus laevis. Loss of CFTR by siRNA-mediated knockdown blunts the RA-induced spermatogonial differentiation. Overexpression of CFTR mimics the effect of RA on the induction of spermatogonial differentiation or restores the developmental defects induced by the knockdown of RARalpha in spermatogonial cells and Xenopus laevis. Analysis of the human database shows that the expression of CFTR positively correlates with RARalpha in brain tissues, stem cells as well as cancers, supporting the role of RA/CFTR pathway in various developmental processes in humans. Together, our study discovers an essential role of CFTR in mediating the RA-dependent signaling for stem cell differentiation and embryonic development.
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