Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
Nucleoporins(Nups)are important components of nuclear pore complexes(NPCs).NPCs control gene expression,cells proliferation and differentiation by mediating exchange of cellular signal molecules on both nuclear and cy...Nucleoporins(Nups)are important components of nuclear pore complexes(NPCs).NPCs control gene expression,cells proliferation and differentiation by mediating exchange of cellular signal molecules on both nuclear and cytoplasmic sides.Using subtractive screening,3'end fragment of Nup93 from the testis cDNA library of the rice field eel was obtained.Full-length cDNA of the gene was further cloned by degenerate PCR and 5'RACE methods.Sequence analysis indicated that the homology of the rice field eel Nup93 were 36.5%with yeast Nic96,94.6%and 90.5%with Nup93 of zebrafish and human,respectively.Phylogenetic analysis showed that the rice field eel Nup93 fits with Nup93 of the other fishes.Real-time PCR result showed that expression of Nup93 in gonads and kidney were much higher than in other tissues,and different expression quantities among gonads of three sexes were also observed,suggesting that Nup93 may involve in gonad development.展开更多
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
基金Supported by the National Natural Science Foundation of China,the National Key Basic Research Project(No.2004CB117400)the Program for New Century Excellent Talents in Universitythe Key Project of Chinese Ministry of Education.
文摘Nucleoporins(Nups)are important components of nuclear pore complexes(NPCs).NPCs control gene expression,cells proliferation and differentiation by mediating exchange of cellular signal molecules on both nuclear and cytoplasmic sides.Using subtractive screening,3'end fragment of Nup93 from the testis cDNA library of the rice field eel was obtained.Full-length cDNA of the gene was further cloned by degenerate PCR and 5'RACE methods.Sequence analysis indicated that the homology of the rice field eel Nup93 were 36.5%with yeast Nic96,94.6%and 90.5%with Nup93 of zebrafish and human,respectively.Phylogenetic analysis showed that the rice field eel Nup93 fits with Nup93 of the other fishes.Real-time PCR result showed that expression of Nup93 in gonads and kidney were much higher than in other tissues,and different expression quantities among gonads of three sexes were also observed,suggesting that Nup93 may involve in gonad development.
