A novel ZnII-based metal-organic framework with the formula of{[Zn_(2)(BBIP)_(2)(NDC)_(2)]·H_(2)O}n(JXUST-5)derived from 3,5-bis(benzimidazol-1-yl)pyridine(BBIP)and 1,4-naphthalenedicarboxylic acid(H_(2)NDC)has b...A novel ZnII-based metal-organic framework with the formula of{[Zn_(2)(BBIP)_(2)(NDC)_(2)]·H_(2)O}n(JXUST-5)derived from 3,5-bis(benzimidazol-1-yl)pyridine(BBIP)and 1,4-naphthalenedicarboxylic acid(H_(2)NDC)has been synthesized.The adjacent Zn^(II)ions are linked through two BBIP ligands to form a[Zn_(2)(BBIP)_(2)]secondary building unit(SBU).The neighbouring SBUs are further connected by NDC^(2-)withμ2-η^(1):η^(1)andμ2-η^(1):η^(1):η^(1)bridging modes to form a two-dimensional(2D)framework.Topological analysis shows that JXUST-5 could be simplified as an uninodal fes topology with a point symbol of{4.8^(2)}.Furthermore,the 2D framework net could be extended through C-H···πinteraction to form the three-dimensional supramolecular structure.Luminescent experiments suggest that JXUST-5 could selectively and sensitively recognize Al^(3+)and Ga^(3+)through fluorescence enhancement effect along with a relatively large red shift.The detection limits for Al^(3+)and Ga^(3+)are 0.17 and 0.69 ppm,respectively.Interestingly,the sensing process for both Al^(3+)and Ga^(3+)could be directly observed with naked eyes under 365 nm UV lamp.Notably,JXUST-5 could be recycled at least five times as a fluorescent sensor toward Al^(3+)and Ga^(3+),which is the second example of turn-on MOF based fluorescent sensor toward Ga^(3+).展开更多
Post-translational modifications(PTMs)are dynamic processes that regulate cell states by enhancing proteome diversity.However,the overall impact of PTMs on pluripotency exit in porcine embryonic stem cells(pESCs)remai...Post-translational modifications(PTMs)are dynamic processes that regulate cell states by enhancing proteome diversity.However,the overall impact of PTMs on pluripotency exit in porcine embryonic stem cells(pESCs)remains largely unknown.Here,we present a systematic assay to identify E3 ubiquitin ligases for pluripotency exit by using CRISPR/Cas9 pooled screening and identified PIAS4 as a major regulator of pluripotency exit,as the cell differentiation was significantly impaired upon PIAS4 depletion in pESCs.PIAS4 shows a high degree of genomic occupation in promoter regions,particularly in key pluripotency maintenance genes.Moreover,we found that PIAS4 was recruited to the gene promoter marked by H3K4me3 and interacted with lysine demethylase KDM5B via SUMOylation,thereby affecting the stability of KDM5B and further facilitating the regulation of H3K4me3-mediated lineage-specific genes.Together,our findings reveal a regulatory mechanism by which PIAS4 modulates H3K4me3 modification on development-related genes,subsequently influencing pluripotency exit and cell fate commitment by interacting with KDM5B in pESCs.展开更多
Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but wh...Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.展开更多
The effective proliferation and differentiation of trophoblast stem cells(TSCs)is indispensable for the development of the placenta,which is the key to maintaining normal fetal growth during pregnancy.Kruppel-like fac...The effective proliferation and differentiation of trophoblast stem cells(TSCs)is indispensable for the development of the placenta,which is the key to maintaining normal fetal growth during pregnancy.Kruppel-like factor 5(Klf5)is implicated in the activation of pluripotency gene expression in embryonic stem cells(ESCs),yet its function in TSCs is poorly understood.Here,we showed that Klf5 knockdown resulted in the downregulation of core TSC-specific genes,consequently causing rapid differentiation of TSCs.Consistently,Klf5-depleted embryos lost the ability to establish TSCs in vitro.At the molecular level,Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes.Deprivation of Klf5 impaired the enrichment of p300,a major histone acetyl transferase of H3 lysine 27 acetylation(H3K27ac),and further reduced the occupancy of H3K27ac at promoter regions,leading to decreased transcriptional activity of TSC pluripotency genes.Thus,our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs and provide a reference for understanding placental development and improving pregnancy rates.展开更多
基金supported from the National Natural Science Foundation of China(Nos.22061019,21761012 and 21861018)the Natural Science Foundation of Jiangxi Province(Nos.20192BAB203001,20202ACBL213001,20192ACBL20013 and 20182BCB22010)+1 种基金the Youth Jinggang Scholars Program in Jiangxi Province(No.QNJG2019053)the Two Thousand Talents Program in Jiangxi Province(No.jxsq2019201068)。
文摘A novel ZnII-based metal-organic framework with the formula of{[Zn_(2)(BBIP)_(2)(NDC)_(2)]·H_(2)O}n(JXUST-5)derived from 3,5-bis(benzimidazol-1-yl)pyridine(BBIP)and 1,4-naphthalenedicarboxylic acid(H_(2)NDC)has been synthesized.The adjacent Zn^(II)ions are linked through two BBIP ligands to form a[Zn_(2)(BBIP)_(2)]secondary building unit(SBU).The neighbouring SBUs are further connected by NDC^(2-)withμ2-η^(1):η^(1)andμ2-η^(1):η^(1):η^(1)bridging modes to form a two-dimensional(2D)framework.Topological analysis shows that JXUST-5 could be simplified as an uninodal fes topology with a point symbol of{4.8^(2)}.Furthermore,the 2D framework net could be extended through C-H···πinteraction to form the three-dimensional supramolecular structure.Luminescent experiments suggest that JXUST-5 could selectively and sensitively recognize Al^(3+)and Ga^(3+)through fluorescence enhancement effect along with a relatively large red shift.The detection limits for Al^(3+)and Ga^(3+)are 0.17 and 0.69 ppm,respectively.Interestingly,the sensing process for both Al^(3+)and Ga^(3+)could be directly observed with naked eyes under 365 nm UV lamp.Notably,JXUST-5 could be recycled at least five times as a fluorescent sensor toward Al^(3+)and Ga^(3+),which is the second example of turn-on MOF based fluorescent sensor toward Ga^(3+).
基金supported by the National Key R&D Program of China(2022YFD1302200)Scientific Innovation 2030 Project(2023ZD04072,2023ZD0404703)+2 种基金the Natural Science Foundation of Hubei Province(2022CFB149)the Fundamental Research Funds for the Central Universities(2662023DKPY001)the Special Research Project on Experimental Animal of Hubei Province(2023CFA006).
文摘Post-translational modifications(PTMs)are dynamic processes that regulate cell states by enhancing proteome diversity.However,the overall impact of PTMs on pluripotency exit in porcine embryonic stem cells(pESCs)remains largely unknown.Here,we present a systematic assay to identify E3 ubiquitin ligases for pluripotency exit by using CRISPR/Cas9 pooled screening and identified PIAS4 as a major regulator of pluripotency exit,as the cell differentiation was significantly impaired upon PIAS4 depletion in pESCs.PIAS4 shows a high degree of genomic occupation in promoter regions,particularly in key pluripotency maintenance genes.Moreover,we found that PIAS4 was recruited to the gene promoter marked by H3K4me3 and interacted with lysine demethylase KDM5B via SUMOylation,thereby affecting the stability of KDM5B and further facilitating the regulation of H3K4me3-mediated lineage-specific genes.Together,our findings reveal a regulatory mechanism by which PIAS4 modulates H3K4me3 modification on development-related genes,subsequently influencing pluripotency exit and cell fate commitment by interacting with KDM5B in pESCs.
基金This work was supported by the National Natural Science Foundation of China(31902161)the National Key Research and Development Program of China(2022YFD1302201,2018YFA0107001)+3 种基金Strategic Priority Research Program of Chinese Academy of Sciences(XDA24020203)Key Research and Development Program of Hubei Province(2021BBA221)Major Project of Hubei Hongshan Laboratory(2021hszd003)Foundation of Key Laboratory of Animal Genetics,Breeding and Reproduction in the Plateau Mountainous Region,Ministry of Education,Guizhou University(QJHKY[2022]373).
文摘Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.
基金This work was supported by the National Natural.Science Foundation of China(31970822 and 31902161)the Key Research and Development Program of Hubei Province(2021BBA221 and 2022BCE002)+1 种基金the Fundamental Research Funds for the Central Universities(2662022DKPY001)the Major Project of Hubei Hongshan Laboratory(2021hszdo03)。
文摘The effective proliferation and differentiation of trophoblast stem cells(TSCs)is indispensable for the development of the placenta,which is the key to maintaining normal fetal growth during pregnancy.Kruppel-like factor 5(Klf5)is implicated in the activation of pluripotency gene expression in embryonic stem cells(ESCs),yet its function in TSCs is poorly understood.Here,we showed that Klf5 knockdown resulted in the downregulation of core TSC-specific genes,consequently causing rapid differentiation of TSCs.Consistently,Klf5-depleted embryos lost the ability to establish TSCs in vitro.At the molecular level,Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes.Deprivation of Klf5 impaired the enrichment of p300,a major histone acetyl transferase of H3 lysine 27 acetylation(H3K27ac),and further reduced the occupancy of H3K27ac at promoter regions,leading to decreased transcriptional activity of TSC pluripotency genes.Thus,our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs and provide a reference for understanding placental development and improving pregnancy rates.
