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Activin Regulates Self-renewal and Differentiation of Trophoblast Stem Cells by Down-regulating the X Chromosome Gene Bcor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2015 Sep 04; Vol. 290 (36), pp. 22019-29. Date of Electronic Publication: 2015 Jul 28. - Publication Year :
- 2015
-
Abstract
- The development of a functional placenta is largely dependent upon proper proliferation and differentiation of trophoblast stem cells (TSCs). Activin signaling has long been regarded to play important roles during this process, but the exact mechanism is largely unknown. Here, we demonstrate that the X chromosome gene BCL-6 corepressor (Bcor) is a critical downstream effector of activin to fine-tune mouse TSC fate decision. Bcor was specifically down-regulated by activin A in TSCs in a dose-dependent manner, and immediately up-regulated upon TSC differentiation. Knockdown of Bcor partially compensated for the absence of activin A in maintaining the self-renewal of TSCs together with FGF4, while promoting syncytiotrophoblast differentiation in the absence of FGF4. Moreover, the impaired trophoblast giant cell and spongiotrophoblast differentiation upon Bcor knockdown also resembled the function of activin. Reporter analysis showed that BCOR inhibited the expression of the key trophoblast regulator genes Eomes and Cebpa by binding to their promoter regions. Our findings provide us with a better understanding of placental development and placenta-related diseases.<br /> (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Animals
Blotting, Western
CCAAT-Enhancer-Binding Proteins genetics
CCAAT-Enhancer-Binding Proteins metabolism
Cell Differentiation genetics
Cell Proliferation genetics
Cells, Cultured
Dose-Response Relationship, Drug
Down-Regulation genetics
Giant Cells drug effects
Giant Cells metabolism
HEK293 Cells
Humans
Mice
Microscopy, Confocal
Promoter Regions, Genetic genetics
Protein Binding
RNA Interference
Repressor Proteins metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells cytology
Stem Cells metabolism
T-Box Domain Proteins genetics
T-Box Domain Proteins metabolism
Trophoblasts cytology
Trophoblasts metabolism
Activins pharmacology
Cell Differentiation drug effects
Cell Proliferation drug effects
Repressor Proteins genetics
Stem Cells drug effects
Trophoblasts drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 290
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26221038
- Full Text :
- https://doi.org/10.1074/jbc.M115.674127