Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understandi...Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking.Here,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were elucidated.Epithelial cells were identified as the most affected cell types by aging in the gingiva.Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal cells.The decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects.Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.展开更多
Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed ...Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.展开更多
Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,sen...Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,senescent cells are known to accumulate across tissues and organs(Sun et al.,2022;Lopez-Otin et al.,2023).展开更多
文摘Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking.Here,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were elucidated.Epithelial cells were identified as the most affected cell types by aging in the gingiva.Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal cells.The decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects.Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+6 种基金the National Natural Science Foundation of China(81921006,92149301,92168201,82125011,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81901432,32000510,81861168034,32000500,81901433,81870228,81922027)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Young Elite Scientists Sponsorship Program by CAST(YESS20200012,YESS20210002)The Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)CAS Project for Young Scientists in Basic Research(YSBR-012),Youth Innovation Promotion Association of CAS(E1CAZW0401,2022083)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14),the Tencent Foundation(2021-1045).
文摘Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
基金supported by the National Key Research and Development Program of China (2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000)+9 种基金the National Natural Science Foundation of China (81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82271600,82192863,32000500,82122024,82071588,32000510)the National Key Research and Development Program of China (2018YFC2000100,2018YFA0107203,2020YFA0112200,2021YFF1201005,the STI2030-Major Projects-2021ZD0202400,2022YFA1103700)CAS Project for Young Scientists in Basic Research (YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation (Z190019)K.C.Wong Education Foundation (GJTD-2019-06,GJTD-2019-08)The Pilot Project for Public Welfare Development and Reform of Beijingaffiliated Medical Research Institutes (11000022T000000461062)Youth Innovation Promotion Association of CAS (E1CAzW0401,2022083)Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301,CASWX2022SDC-XK14,CAS-WX2021SF-0101)the Tencent Foundation (2021-1045).
文摘Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,senescent cells are known to accumulate across tissues and organs(Sun et al.,2022;Lopez-Otin et al.,2023).
