Background:Tooth is vital not only for a good smile,but also good health.Yet,we lose tooth regularly due to accidents or diseases.An ideal solution to this problem is to regenerate tooth with patients’own cells.Here ...Background:Tooth is vital not only for a good smile,but also good health.Yet,we lose tooth regularly due to accidents or diseases.An ideal solution to this problem is to regenerate tooth with patients’own cells.Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells(ifhU-iPSCs).Results:We first differentiated ifhU-iPSCs to epithelial sheets,which were then recombined with E14.5 mouse dental mesenchymes.Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30%for 8 different iPSC lines,comparable to H1 hESC.We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures,possessing physical properties such as elastic modulus and hardness found in the regular human tooth.Conclusion:Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.展开更多
Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps...Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesisin mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially duringearly embryonic development stage, is largely unknown.Results: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout humanembryonic stem cells (GATA2^(−/−) hESCs) and analyzed their blood differentiation potential. Our results demonstratedthat GATA2^(−/−) hESCs displayed attenuated generation of CD34^(+)CD43^(+) hematopoietic progenitor cells (HPCs), due tothe impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2^(−/−) hESCs retained the potentialto generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulationwas partially responsible for the defects of GATA2^(−/−) hESCs in generation of CD34^(+)CD43^(+) HPCs and granulocytes.Furthermore, we found that GATA2^(−/−) hESCs restored the granulocyte potential in the presence of Notch signaling.Conclusion: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development throughregulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled byhuman ESCs.展开更多
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
Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PR...Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PRC1 and PRC2.PRC1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019).PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).展开更多
基金We thank Prof.Yanding Zhang and Prof.Dajiang Qin for valuable suggestions and all staffs working for the South Stem Cell Bank.This work was supported by the grants from Ministry of Science and Technology 973 Program(2010CB944800,2011CB965200)National Natural Science Foundation of China(31000402)+3 种基金the“Strategic Priority Research Program”of the Chinese Academy of Sciences(XDA01020401,XDA01020202)863 Program(2011AA020109)Ministry of Science and Technology International Technology Cooperation Program(2012DFH30050)Open Project of Key Laboratory of Regenerative Biology,Chinese Academy of Sciences(KLRB201217).
文摘Background:Tooth is vital not only for a good smile,but also good health.Yet,we lose tooth regularly due to accidents or diseases.An ideal solution to this problem is to regenerate tooth with patients’own cells.Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells(ifhU-iPSCs).Results:We first differentiated ifhU-iPSCs to epithelial sheets,which were then recombined with E14.5 mouse dental mesenchymes.Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30%for 8 different iPSC lines,comparable to H1 hESC.We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures,possessing physical properties such as elastic modulus and hardness found in the regular human tooth.Conclusion:Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.
基金This work was supported by the following:National Basic Research Program of China,973 Program of China(2012CB966503,2011CB965204,2014CB964604)“Strategic Priority Research Program”of the Chinese Academy of Sciences Grant No.XDA01020202+3 种基金National Natural Science Foundation of China(31371514,31200970,81301340)National Natural Science Foundation-Guangdong Joint Fund No.U1132005,National S&T Major Special Project on Major New Drug Innovation,Grant No.2011ZX09102010“Hundred Talents Program”of Chinese Academy of Sciences(to Dr.G Pan)the Equipment Function Development&Technology Innovation Project of the Chinese Academy of Sciences(Grant Nos.yg2012049,yg2011082,and yg2011083)。
文摘Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesisin mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially duringearly embryonic development stage, is largely unknown.Results: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout humanembryonic stem cells (GATA2^(−/−) hESCs) and analyzed their blood differentiation potential. Our results demonstratedthat GATA2^(−/−) hESCs displayed attenuated generation of CD34^(+)CD43^(+) hematopoietic progenitor cells (HPCs), due tothe impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2^(−/−) hESCs retained the potentialto generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulationwas partially responsible for the defects of GATA2^(−/−) hESCs in generation of CD34^(+)CD43^(+) HPCs and granulocytes.Furthermore, we found that GATA2^(−/−) hESCs restored the granulocyte potential in the presence of Notch signaling.Conclusion: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development throughregulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled byhuman ESCs.
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.
基金supported by the National Natural Science Foundation of China(31925009,U21A20195)the National Key Research and Development Program of China(2021YFA1100300)。
文摘Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PRC1 and PRC2.PRC1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019).PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).
