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
Background:Zinc finger protein of cerebellum 2(ZIC2)is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system.Previous studies have reported that ZIC2 is widely ...Background:Zinc finger protein of cerebellum 2(ZIC2)is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system.Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors.Methods:Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular car-cinoma(HCC)and normal liver tissues.Quantitative real-time polymerase chain reaction and immu-nohistochemistry were conducted to validate the results from the database.Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC.Results:Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues.In addition,patients with high ZIC2 levels had a poor prognosis.Multivariate analysis showed that clinical stage(T or M classification)and ZIC2 levels were independent prognostic factors for overall survival.Moreover,a subgroup analysis revealed that patients with moderate or poor grade tumors,T1e2 tumors,N0 tumors,early American Joint Committee on Cancer(AJCC)stage,and old age were more likely to present with overexpression of ZIC2.To conclude,ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients.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This work was supported by the National Natural Science Foundation of China(81702375 to K.Hu)Natural Science Foun-dation of Guangdong Province,China(2016A030313200 to K.Hu).
文摘Background:Zinc finger protein of cerebellum 2(ZIC2)is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system.Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors.Methods:Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular car-cinoma(HCC)and normal liver tissues.Quantitative real-time polymerase chain reaction and immu-nohistochemistry were conducted to validate the results from the database.Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC.Results:Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues.In addition,patients with high ZIC2 levels had a poor prognosis.Multivariate analysis showed that clinical stage(T or M classification)and ZIC2 levels were independent prognostic factors for overall survival.Moreover,a subgroup analysis revealed that patients with moderate or poor grade tumors,T1e2 tumors,N0 tumors,early American Joint Committee on Cancer(AJCC)stage,and old age were more likely to present with overexpression of ZIC2.To conclude,ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients.
