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| 1 | Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome显示文摘Hutchinson-Gilford 早衰症候群(HGPS ) 和沃纳症候群(WS ) 是二最好描绘的人的 progeroid 症候群。HGPS 被一个点变化在 lamin A (LMNA ) 基因引起,导致截断的蛋白质 productprogerin 的生产。WS 被变化在 WRN 基因引起,编码 loss-of-function RecQ DNA helicase。这里,由基因编辑,我们创造了 isogenic 人的胚胎的干细胞(转换字符) 与异质接合(G608G/+) 或同型结合(G608G/G608G ) LMNA 变化和 biallelic WRN 大美人为为 HGPS 和 WS 致病建模,分别地。当转换字符和 endothelial 房间(EC ) 没介绍早熟的老朽的任何特征时, HGPS 间充质、 WS 间充质的干细胞(MSC ) 与不同动力学显示出联系老化的显型。当 HGPS-MSCs 展出了迟了发作的尖锐早衰 characterisitcs 时, WS-MSCs 有早发作的温和早衰显型。一起拿,我们的学习比较并且形成对照不同病理 underpinning 二早衰混乱,并且提供可靠干细胞为病理学、生理的老化识别新治疗学的策略的基于的模型。 | 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 | 2018 | Protein & Cell2018，9，4： | 15 |
| 2 | Chemical screen identifies a geroprotective role of quercetin in premature aging显示文摘Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders. | Lingling Geng Zunpeng Liu Weiqi Zhang Wei Li Zeming Wu Wei Wang Ruotong Ren Yao Su Peichang Wang Liang Sun Zhenyu Ju Piu Chan Moshi Song Jing Qu Guang-Hui Liu | 2019 | Protein & Cell2019，10，6： | 13 |
| 3 | Single-cell transcriptomic atlas of primate cardiopulmonary aging显示文摘Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019(COVID-19).Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed.Here,we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung,heart and artery,the top tissues targeted by SARS-CoV-2.Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging.With age,expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2(ACE2)was increased in the pulmonary alveolar epithelial barrier,cardiomyocytes,and vascular endothelial cells.We found that interleukin 7(IL7)accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner.Furthermore,treatment with vitamin C blocked IL7-induced ACE2 expression.Altogether,our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2,suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly. | Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu | 2021 | Cell Research2021，31，4： | 10 |
| 4 | SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer显示文摘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,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated 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. | 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 | 2020 | Protein & Cell2020，11，7： | 10 |
| 5 | Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration显示文摘Accumulating evidence indicates an association between the circadian clock and the aging process.However,it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes.Here,we identified a transcription factor-independent role of CLOCK,a core component of the molecular circadian clock machinery,in counteracting human mesenchymal stem cell(hMSC)decay.CLOCK expression was decreased during hMSC aging.In addition,CLOCK deficiency accelerated hMSC senescence,whereas the overexpression of CLOCK,even as a transcriptionally inactive form,rejuvenated physiologically and pathologically aged hMSCs.Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1,thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences.Finally,gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice.These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin,promoting tissue regeneration,and mitigating aging-associated chronic diseases. | Chuqian Liang Zunpeng Liu Moshi Song Wei Li Zeming Wu Zehua Wang Qiaoran Wang Si Wang Kaowen Yan Liang Sun Tomoaki Hishida Yanning Cai Juan Carlos lzpisua Belmonte Pedro Guillen Piu Chan Qi Zhou Weiqi Zhang Jing Qu Guang-Hui Liu | 2021 | Cell Research2021，31，2： | 8 |
| 6 | Exosomes from antler stem cells alleviate mesenchymal stem cell senescence and osteoarthritis显示文摘Dear Editor,Stem cell therapy holds enormous and revolutionary promise to treat various age-related diseases,such as diabetes,heart failure,and Parkinson’s disease.However,low retention and survival rate of delivered stem cells,partially due to immunological rejection,constitute major hurdles for the clinical implementation of stem cell therapy(Lei et al.,2021a).Since mounting evidence showed that several types of stem cells mainly exert their therapeutic effects through the secretion of paracrine effects,exosomes,which are released by stem cells and execute most paracrine functions,have begun to draw attention in the field(Tran and Damaser,2015).Exosomes are membrane-enclosed vesicles with an average diameter of∼100 nanometers secreted by the cells,containing cytokines. | Jinghui Lei Xiaoyu Jiang Wei Li Jie Ren Datao Wang Zhejun Ji Zeming Wu Fang Cheng Yusheng Cai Zheng-Rong Yu Juan Carlos Izpisua Belmonte Chunyi Li Guang-Hui Liu Weiqi Zhang Jing Qu Si Wang | 2022 | Protein & Cell2022，13，3： | 1 |
| 7 | Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells显示文摘Dear Editor,The interventions that slow aging or promote healthy aging may provide preventative measures for age-related diseases(Zhang et al.,2015).Therefore,it is crucial to identify drugs that target aging-related pathologies and improve health-span in geroscience research.Using model organisms such as C.elegans and rodents,several small molecules capable of alleviating the onset or progression of aging,including rapamycin,nicotinamide mononucleotide,and metformin,have been discovered(Partridge et al.,2020).However,the safety and efficacy of these chemicals still need in-depth evaluation before clinical applications(Partridge et al.,2020).As a result,it is necessary to identify additional compounds with geroprotective effects for human cells to counteract the general trend of populational aging.However,transforming a promising compound into an approved drug requires enormous resources.Alternatively,repurposing previously approved drugs for new clinical applications offers a more efficient and less costly path toward drug develop-ment.Therefore,testing U.S.Food and Drug Administration(FDA)-approved drugs for geroprotective effects may dis-covernew therapeutics that have already been stringently tested in humans for safety. | Hezhen Shan Lingling Geng Xiaoyu Jiang Moshi Song Jianxun Wang Zunpeng Liu Xiao Zhuo Zeming Wu Jianli Hu Zhejun Ji Si Wang Piu Chan Jing Qu Weiqi Zhang Guang-Hui Liu | 2022 | Protein & Cell2022，13，7： | 1 |
| 8 | Convenient and efficient access to tri-and tetra-substituted 4-fluoropyridines via a[3+2]/[2+1]cyclization reaction显示文摘A[3+2]/[2+1]cycloaddition reaction of gem–difluorocyclopropenes is presented,offering a mild and efficient approach to accessing tri-and tetra-substituted 4-fluoropyridines in moderate to good yields with excellent regioselectivity.Multiple synthetic applications,including process-scale reactions,modification of bioactive molecules,derivatization reactions and synthesis of the analogue of the PKM2 modulator,are subsequently described. | Xuejiao Tang Kun Liu Zeming Qu Junyan Zhan Rukui Zhu Fan Teng Lili Meng Yanmin Huang Chusheng Huang Yimiao He Qiang Zhu | 2022 | Chinese Chemical Letters2022，33，6： | 1 |
| 9 | Hyperthermia differentially affects specific human stem cells and their differentiated derivatives显示文摘Dear Editor,The human body operates optimally at a core temperature of 37 degrees Celsius.Homeostasis at this temperature is essential for cellular and physiological functions(Cheshire,2016).However,infectious diseases,inflammation,injury,neoplasia,and elevated climate temperature can cause a regulated rise in body core temperature,i.e.,fever(Pasi-khova et al,2017).Indeed,an acute or chronic increase in temperature leads to detrimental effects on vasculature by altering a number of indices of vascular structure and function(DuBose et al.,1998). | Si Wang Fang Cheng Qianzhao Ji Moshi Song Zeming Wu Yiyuan Zhang Zhejun Ji Huyi Feng Juan Carlos Izpisua Belmonte Qi Zhou Jing Qu Wei Li Guang-Hui Liu Weiqi Zhang | 2022 | Protein & Cell2022，13，8： | 0 |
| 10 | FTO stabilizes MIS12 and counteracts senescence显示文摘Dear Editor, N6-methyladenosine(m6A)is an abundant epitranscriptomic modification that regulates messenger RNA(mRNA)biology.The m6A modification regulates mRNA splicing,transport,stability,and translation through coordinated activities by methyltransferases(writers),binding proteins(readers),and demethylases(erasers)(Huang et al.,2020;Wu et al.,2020).Among m6A regulators,fat mass of obesity-associ-ated protein(FTO),is the first discovered eraser with RNA m6A demethylation activity(Jia et al.,2011).Since then,FTO has been reported to play m6A-dependent roles in a variety of physiological processes including adipogenesis,neuro-genesis and tumorigenesis(Fischer et al.,2009;Li et al.,2017;Huang et al.,2020).Consequently,FTO deficiency in mice leads to dramatic phenotypes,such as decreased fat mass and impaired brain development(Fischer et al.,2009;Li et al.,2017).Similarly,inhibition of FTO reduces tumori-genesis in multiple types of cancer models,while FTO is highly expressed in many cancers(Huang et al.,2020). | Sheng Zhang Zeming Wu Yue Shi Si Wang Jie Ren Zihui Yu Daoyuan Huang Kaowen Yan Yifang He Xiaoqian Liu Qianzhao Ji Beibei Liu Zunpeng Liu Jing Qu Guang-Hui Liu Weimin Ci Xiaoqun Wang Weiqi Zhang | 2022 | Protein & Cell2022，13，12： | 0 |
| 11 | ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells显示文摘Dear Editor,As the most prevalent DNA methylation modification in prokaryotes,DNA N6 methyladenosine(6mA)in eukaryotic genomes has recently been observed in diverse species including Caenorhabditis elegans(Greer et al.,2015),Dro-sophila melanogaster(Zhang et al,2015),mouse(Wu et al,2016)and human(Xiao et al,2018).6mA has been reported to associate with multiple physiological processes including embryonic development and tumorigenesis(Greer et al.,2015;Zhang et al.,2015;Xie et al.,2018),yet some con-troversies exist.In contrast to the findings showing that ALKBH1(alkB homolog 1)is a primary 6mA demethylase in mouse and human cells(Wu et al.,2016;Xiao et al.,2018;Xie et al..2018),other studies indicate that ALKBH1 is prone to demethylate 6mA on bubbled or bulged DNAs that are often featured by a locally unpairing region with flanking duplex,such as D-loop,R-loop as well as DNA or RNA stem-loop,and single-stranded DNAs at a lower efficiency. | 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 | 2020 | Protein & Cell2020，11，9： | 0 |
| 12 | Study on the Active Phases of Ni-W System Hydrotreating Catalysts显示文摘StudyontheActivePhasesofNiWSystemHydrotreatingCatalystsShiYahua,QuLianglong,WuDingjun,JinZeming,LiDadong(ResearchInstituteo... | Shi Yahua, Qu Lianglong, Wu Dingjun, Jin Zeming, Li Dadong Part of the work were done by Xue Yongfang, and Sun Naijian. (Research Institute of Petroleum Processing, Beijing 100083) | 1997 | 石油学报(石油加工)1997，13，S1： | 0 |
| 13 | 4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis显示文摘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 celis(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 findings 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 Il,thus providing a new potential target to counteract human stem cell senescence. | 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 | 2023 | Protein & Cell2023，14，3： | 0 |
| 14 | Rhodium-catalyzed formal[4+3]annulation reaction of N-methoxybenzamides with gem–difluorocyclopropenes:A combination of experimental and theoretical studies显示文摘A rhodium-catalyzed[4+3]cycloaddition reaction between N-methoxybenzamides and gem–difluorocyclopropenes is described.The reaction offers a mild and efficient approach towards the synthesis of fluorinated 2 H-azepin-2-ones with broad substrate scope.A consecutive HOAc-assisted C–N bond formation and fluorine elimination are involved as key steps for success as illustrated by detailed DFT studies. | Yimiao He Limei Tian Xuexue Chang Zeming Qu Yanmin Huang Chusheng Huang Qing Sun Honggen Wang | 2022 | Chinese Chemical Letters2022，33，6： | 0 |
| 15 | APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation显示文摘Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood. | 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 | 2023 | Protein & Cell2023，14，12： | 0 |
| 16 | mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic,mesenchymal and neural stem cells显示文摘Dear Editor,Stem cells,including pluripotent stem cells and adult stem cells,possess the remarkable capability of being able to selfrenew while at the same time having potential to differentiate into different cell lineages and functionally distinct cell types.Human embryonic stem cells(hESCs)can differentiate into all adult stem cell types,including human mesenchymal stem cells(hMSCs)and human neural stem cells(hNSCs),but can also give rise to all terminally differentiated cell types(Wang et al.,2021a).Through the continuous replenishment of differentiated cells,stem cells support tissue homeostasis and respond to tissue injuries.Given the promising applications of stem cells in cell therapy and regenerative medicine,insights into molecular events underlying stem cell maintenance,self-renewal ability and pluripotency,continue to garner strong interest(Shan et al.,2021).Although metabolic pathways have been implicated in the reciprocal regulations of stem cell self-renewal and differentiation as well as organ homeostatic maintenance(Garcia-Prat et al.,2017),central aspects of how metabolic requirements differ and are regulated across the various types of human stem cells in our body remain enigmatic. | Qun Chu Feifei Liu Yifang He Xiaoyu Jiang Yusheng Cai Zeming Wu Kaowen Yan Lingling Geng Yichen Zhang Huyi Feng Kaixin Zhou Si Wang Weiqi Zhang Guang-Hui Liu Shuai Ma Jing Qu Moshi Song | 2022 | Protein & Cell2022，13，9： | 0 |
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