1.Basic and translational aging research in China: present and future.
Xiaojuan HE ; Moshi SONG ; Jing QU ; Yansu GUO ; Heqi CAO ; Ruijuan SUN ; Guang-Hui LIU ; Yong SHEN ; Major Program Expert Group
Protein & Cell 2019;10(7):476-484
2.ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells.
Hongyu LI ; Zeming WU ; Xiaoqian LIU ; Sheng ZHANG ; Qianzhao JI ; Xiaoyu JIANG ; Zunpeng LIU ; Si WANG ; Jing QU ; Weiqi ZHANG ; Moshi SONG ; Eli SONG ; Guang-Hui LIU
Protein & Cell 2020;11(9):688-695
3.DJ-1 is dispensable for human stem cell homeostasis.
Fang CHENG ; Si WANG ; Moshi SONG ; Zunpeng LIU ; Ping LIU ; Lei WANG ; Yanjiang WANG ; Qian ZHAO ; Kaowen YAN ; Piu CHAN ; Weiqi ZHANG ; Jing QU ; Guang-Hui LIU
Protein & Cell 2019;10(11):846-853
4.Low-dose quercetin positively regulates mouse healthspan.
Lingling GENG ; Zunpeng LIU ; Si WANG ; Shuhui SUN ; Shuai MA ; Xiaoqian LIU ; Piu CHAN ; Liang SUN ; Moshi SONG ; Weiqi ZHANG ; Guang-Hui LIU ; Jing QU
Protein & Cell 2019;10(10):770-775
5.CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells.
Ping WANG ; Zunpeng LIU ; Xiaoqian ZHANG ; Jingyi LI ; Liang SUN ; Zhenyu JU ; Jian LI ; Piu CHAN ; Guang-Hui LIU ; Weiqi ZHANG ; Moshi SONG ; Jing QU
Protein & Cell 2018;9(11):945-965
Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NF-κB regulates human blood vessel homeostasis remains largely elusive. Here, using CRISPR/Cas9-mediated gene editing, we generated RelA knockout human embryonic stem cells (hESCs) and differentiated them into various vascular cell derivatives to study how NF-κB modulates human vascular cells under basal and inflammatory conditions. Multi-dimensional phenotypic assessments and transcriptomic analyses revealed that RelA deficiency affected vascular cells via modulating inflammation, survival, vasculogenesis, cell differentiation and extracellular matrix organization in a cell type-specific manner under basal condition, and that RelA protected vascular cells against apoptosis and modulated vascular inflammatory response upon tumor necrosis factor α (TNFα) stimulation. Lastly, further evaluation of gene expression patterns in IκBα knockout vascular cells demonstrated that IκBα acted largely independent of RelA signaling. Taken together, our data reveal a protective role of NF-κB/RelA in modulating human blood vessel homeostasis and map the human vascular transcriptomic landscapes for the discovery of novel therapeutic targets.
Blood Vessels
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cytology
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metabolism
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CRISPR-Cas Systems
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Embryonic Stem Cells
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cytology
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Gene Knockout Techniques
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Homeostasis
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Humans
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NF-kappa B
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deficiency
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metabolism
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Transcription Factor RelA
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deficiency
;
metabolism
6.Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome.
Zeming WU ; Weiqi ZHANG ; Moshi SONG ; Wei WANG ; Gang WEI ; Wei LI ; Jinghui LEI ; Yu HUANG ; Yanmei SANG ; Piu CHAN ; Chang CHEN ; Jing QU ; Keiichiro SUZUKI ; Juan Carlos Izpisua BELMONTE ; Guang-Hui LIU
Protein & Cell 2018;9(4):333-350
Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging.
Aging
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genetics
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physiology
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DNA Helicases
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genetics
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Human Embryonic Stem Cells
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metabolism
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physiology
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Humans
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Kinetics
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Lamin Type A
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genetics
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Mesenchymal Stem Cells
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metabolism
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physiology
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Mutation
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Progeria
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genetics
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physiopathology
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Werner Syndrome
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genetics
;
physiopathology
7.SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer.
Shijia BI ; Zunpeng LIU ; Zeming WU ; Zehua WANG ; Xiaoqian LIU ; Si WANG ; Jie REN ; Yan YAO ; Weiqi ZHANG ; Moshi SONG ; Guang-Hui LIU ; Jing QU
Protein & Cell 2020;11(7):483-504
SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.
8.APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation.
Hongkai ZHAO ; Kuan YANG ; Yiyuan ZHANG ; Hongyu LI ; Qianzhao JI ; Zeming WU ; Shuai MA ; Si WANG ; Moshi SONG ; Guang-Hui LIU ; Qiang LIU ; Weiqi ZHANG ; Jing QU
Protein & Cell 2023;14(12):908-913
9.4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis.
Yifang HE ; Qianzhao JI ; Zeming WU ; Yusheng CAI ; Jian YIN ; Yiyuan ZHANG ; Sheng ZHANG ; Xiaoqian LIU ; Weiqi ZHANG ; Guang-Hui LIU ; Si WANG ; Moshi SONG ; Jing QU
Protein & Cell 2023;14(3):202-216
Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology*
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Cellular Senescence
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Homeostasis
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Cell Cycle Proteins/metabolism*
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Adaptor Proteins, Signal Transducing/metabolism*
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Mitochondria/metabolism*
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Electron Transport Complex III/metabolism*
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Humans
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Cells, Cultured
10.Gut microbial methionine impacts circadian clock gene expression and reactive oxygen species level in host gastrointestinal tract.
Xiaolin LIU ; Yue MA ; Ying YU ; Wenhui ZHANG ; Jingjing SHI ; Xuan ZHANG ; Min DAI ; Yuhan WANG ; Hao ZHANG ; Jiahe ZHANG ; Jianghua SHEN ; Faming ZHANG ; Moshi SONG ; Jun WANG
Protein & Cell 2023;14(4):309-313