Polycomb repressive complexes(PRCs)are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells(hESCs),but the underlying molecular basis remains unclear.Here in this study,by employin...Polycomb repressive complexes(PRCs)are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells(hESCs),but the underlying molecular basis remains unclear.Here in this study,by employing an array of different approaches,such as gene knock-out,RNA-seq,ChIP-seq,et al.,we uncover that EZH2,an important PRC factor,specifies the normal neural fate decision through repressing the competing meso/endoderm program.EZH2^(−/−)hESCs show an aberrant re-activation of meso/endoderm genes during neural induction.At the molecular level,EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate.Moreover,EZH2 also supports the proliferation of human neural progenitor cells(NPCs)through repressing the aberrant expression of meso/endoderm program during culture.Together,our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.展开更多
基金This work was granted by the National Key Research and Development Program of China,Stem Cell and Translational Research(2017YFA0102600)Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA16030504)+8 种基金the National Natural Science Foundation of China(31801220,31971374)Science and Technology Planning Project of Guangdong Province,China(2017B030314056)the Frontier and Key Technology Innovation Special Grant from the Department of Science and Technology of Guangdong Province(2016B030230002,2016B030229008)the Natural Science Foundation of Guangdong Province,China(2020A1515010139)Guangzhou Science and Technology Program General project(20180304001,201904020045,201904010462)Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104005)the Informationization Special Project of Chinese Academy of Sciences“E-Science Application for Knowledge Discovery in Stem Cells(XXH13506-203)the Open Research Funds of the State Key Laboratory of Ophthalmology(2019KF06)the Guangdong Province Special Program for Outstanding Talents(to G.P.,2019JC05Y463).
文摘Polycomb repressive complexes(PRCs)are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells(hESCs),but the underlying molecular basis remains unclear.Here in this study,by employing an array of different approaches,such as gene knock-out,RNA-seq,ChIP-seq,et al.,we uncover that EZH2,an important PRC factor,specifies the normal neural fate decision through repressing the competing meso/endoderm program.EZH2^(−/−)hESCs show an aberrant re-activation of meso/endoderm genes during neural induction.At the molecular level,EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate.Moreover,EZH2 also supports the proliferation of human neural progenitor cells(NPCs)through repressing the aberrant expression of meso/endoderm program during culture.Together,our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.
