Foxd3 suppresses NFAT-mediated differentiation to maintain self-renewal of embryonic stem cells.
Pluripotency-associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, molecular mechanisms underlying its function are largely unknown. Here, we report that Foxd3 suppresses differentiation induced by calcineurin-NFAT signaling to maintain the ESC identity. Mechanistically, Foxd3 interacts with NFAT proteins and recruits co-repressor Tle4, a member of the Tle repressor family highly expressed in undifferentiated ESCs, to suppress NFATc3's transcriptional activities. Furthermore, global transcriptome analysis shows that Foxd3 and NFATc3 co-regulate a set of differentiation-associated genes in ESCs. Collectively, our study establishes a molecular and functional link between a pluripotency-associated factor and an important ESC differentiation-inducing pathway.
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes of Biological Sciences Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.
Lili
L
Zhu
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes of Biological Sciences Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China University of Chinese Academy of Sciences, Beijing, China.
Shiyue
S
Zhang
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes of Biological Sciences Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China Shanghai Stem Cell Institute, Shanghai JiaoTong University School of Medicine, Shanghai, China yjin@sibs.ac.cn.
Ying
Y
Jin
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008962:Models, Theoretical; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; D050778:NFATC Transcription Factors; D012097:Repressor Proteins
Foxd3; NFAT; embryonic stem cells