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

Xiaofeng Li, Kin Lam Fok, Jinghui Guo, Yan Wang, Zhenqing Liu, Ziyi Chen, Chengdong Wang, Yechun Ruan, Sidney Siubun Yu, Hui Zhao, Ji Wu, Xiaohua Jiang, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

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 RARα 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 RARα in spermatogonial cells and Xenopus laevis. Analysis of the human database shows that the expression of CFTR positively correlates with RARα 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.

Original languageEnglish
Pages (from-to)605-615
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1865
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018
Externally publishedYes

Keywords

  • CFTR
  • Development
  • Differentiation
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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