The pluripotent state of embryonic stem cells(ESCs)is regulated by a sophisticated network of transcription factors.High expression of KLF17 has recently been identified as a hallmark of naive state of human ESCs(h ES...The pluripotent state of embryonic stem cells(ESCs)is regulated by a sophisticated network of transcription factors.High expression of KLF17 has recently been identified as a hallmark of naive state of human ESCs(h ESCs).However,the functional role of KLF17 in naive state is not clear.Here,by employing various gain and loss-of-function approaches,we demonstrate that KLF17 is essential for the maintenance of naive state and promotes the primed to naive state transition in h ESCs.Mechanistically,we identify MAPK3 and ZIC2 as two direct targets repressed by KLF17.Overexpression of MAPK3 or ZIC2 partially blocks KLF17 from promoting the naive pluripotency.Furthermore,we find that human and mouse homologs of KLF17 retain conserved functions in promoting naive pluripotency of both species.Finally,we show that Klf17 may be essential for early embryo development in mouse.These findings demonstrate the important and conserved function of KLF17 in promoting naive pluripotency and reveal two essential transcriptional targets of KLF17 that underlie its function.展开更多
Dear Editor,Cell-fate decisions are governed by comprehensive generegulatory programs.During the preimplantation development,at least two waves of cell fate decisions are made while the cells gradually lose their toti...Dear Editor,Cell-fate decisions are governed by comprehensive generegulatory programs.During the preimplantation development,at least two waves of cell fate decisions are made while the cells gradually lose their totipotency(Schrode et al.,2013).The first decision involves the spatial separation of outer-residing trophectoderm(TE)cells from inner cell mass(ICM)in E3.5 mouse blastocyst.The second decision involves gene expression refinements and active cell sorting within the ICM that ultimately results in epiblast(EPI)cells,residing deep within the ICM,and the primitive endoderm(PrE)cells comprising a monolayer of blastocoel-facing cells at the surface of the ICM(Schrode et al.,2013).OCT4,SOX2,and NANOG are master transcription factors(TFs)essential for the formation and maintenance of the pluripotent ICM cells and their in vitro counterparts mouse embryonic stem cells(ESCs).On the other hand,GATA4,GATA6,and SOX17 are master TFs of the PrE cells and their in vitro counterparts extraembryonic endoderm stem cells(XENs).展开更多
CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-020-00775-X In the original publication the labelling in middle and bottom panels of Fig.2K is published incorrectly as“Soc17”.The correct labeling is availa...CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-020-00775-X In the original publication the labelling in middle and bottom panels of Fig.2K is published incorrectly as“Soc17”.The correct labeling is available in this correction as“Sox17”.展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0107601 and2021YFA0100200)the National Natural Science Foundation of China(91940302,32130017,82070294 and 32025007)。
文摘The pluripotent state of embryonic stem cells(ESCs)is regulated by a sophisticated network of transcription factors.High expression of KLF17 has recently been identified as a hallmark of naive state of human ESCs(h ESCs).However,the functional role of KLF17 in naive state is not clear.Here,by employing various gain and loss-of-function approaches,we demonstrate that KLF17 is essential for the maintenance of naive state and promotes the primed to naive state transition in h ESCs.Mechanistically,we identify MAPK3 and ZIC2 as two direct targets repressed by KLF17.Overexpression of MAPK3 or ZIC2 partially blocks KLF17 from promoting the naive pluripotency.Furthermore,we find that human and mouse homologs of KLF17 retain conserved functions in promoting naive pluripotency of both species.Finally,we show that Klf17 may be essential for early embryo development in mouse.These findings demonstrate the important and conserved function of KLF17 in promoting naive pluripotency and reveal two essential transcriptional targets of KLF17 that underlie its function.
基金We thank Dr.Philippe Soriano for providing the XENB1 cell line.Research in Wang laboratory was funded by grants from the NIH(R01GM129157,R01HD095938,and R01HD097268)and NYSTEM(C32583GG and C32569GG).
文摘Dear Editor,Cell-fate decisions are governed by comprehensive generegulatory programs.During the preimplantation development,at least two waves of cell fate decisions are made while the cells gradually lose their totipotency(Schrode et al.,2013).The first decision involves the spatial separation of outer-residing trophectoderm(TE)cells from inner cell mass(ICM)in E3.5 mouse blastocyst.The second decision involves gene expression refinements and active cell sorting within the ICM that ultimately results in epiblast(EPI)cells,residing deep within the ICM,and the primitive endoderm(PrE)cells comprising a monolayer of blastocoel-facing cells at the surface of the ICM(Schrode et al.,2013).OCT4,SOX2,and NANOG are master transcription factors(TFs)essential for the formation and maintenance of the pluripotent ICM cells and their in vitro counterparts mouse embryonic stem cells(ESCs).On the other hand,GATA4,GATA6,and SOX17 are master TFs of the PrE cells and their in vitro counterparts extraembryonic endoderm stem cells(XENs).
文摘CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-020-00775-X In the original publication the labelling in middle and bottom panels of Fig.2K is published incorrectly as“Soc17”.The correct labeling is available in this correction as“Sox17”.
