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| 1 | Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing显示文摘Many human genetic diseases,including Hutchinson-Gilford progeria syndrome(HGPS),are caused by single point mutations.HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene.Base editors(BEs)composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions.Here,we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA(gRNA)targeting the LMNA gene via microinjection into monkey zygotes.Five out of six newborn monkeys carried the mutation specifically at the target site.HGPS monkeys expressed the toxic form of lamin A,progerin,and recapitulated the typical HGPS phenotypes including growth retardation,bone alterations,and vascular abnormalities.Thus,this monkey model genetically and clinically mimics HGPS in humans,demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates. | Fang Wang Weiqi Zhang Qiaoyan Yang Yu Kang Yanling Fan Jingkuan Wei Zunpeng Liu Shaoxing Dai Hao Li Zifan Li Lizhu Xu Chu Chu Jing Qu Chenyang Si Weizhi Ji Guang-Hui Liu Chengzu Long Yuyu Niu | 2020 | Protein & Cell2020，11，11： | 11 |
| 2 | A human circulating immune cell landscape in aging and COVID-19显示文摘Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly. | Yingfeng Zheng Xiuxing Liu Wenqing Le Lihui Xie He Li Wen Wen Si Wang Shuai Ma Zhaohao Huang Jinguo Ye Wen Shi Yanxia Ye Zunpeng Liu Moshi Song Weiqi Zhang Jing-Dong J.Han Juan Carlos lzpisua Belmonte Chuanle Xiao Jing Qu Hongyang Wang Guang-Hui Liu Wenru Su | 2020 | Protein & Cell2020，11，10： | 10 |
| 3 | 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 |
| 4 | The landscape of aging显示文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels. | Yusheng Cai Wei Song Jiaming Li Ying Jing Chuqian Liang Liyuan Zhang Xia Zhang Wenhui Zhang Beibei Liu Yongpan An Jingyi Li Baixue Tang Siyu Pei Xueying Wu Yuxuan Liu Cheng-Le Zhuang Yilin Ying Xuefeng Dou Yu Chen Fu-Hui Xiao Dingfeng Li Ruici Yang Ya Zhao Yang Wang Lihui Wang Yujing Li Shuai Ma Si Wang Xiaoyuan Song Jie Ren Liang Zhang Jun Wang Weiqi Zhang Zhengwei Xie Jing Qu Jianwei Wang Yichuan Xiao Ye Tian Gelin Wang Ping Hu Jing Ye Yu Sun Zhiyong Mao Qing-Peng Kong Qiang Liu Weiguo Zou Xiao-Li Tian Zhi-Xiong Xiao Yong Liu Jun-Ping Liu Moshi Song Jing-Dong J.Han Guang-Hui Liu | 2022 | Science China(Life Sciences)2022，65，12： | 4 |
| 5 | A single-cell transcriptomic atlas of primate pancreatic islet aging显示文摘Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes.Endocrine cells age heterogeneously,complicating the efforts to unravel the molecular drivers underlying endocrine aging.To overcome these obstacles,we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys.Despite sex differences and increased transcriptional variations,agedβ-cells showed increased unfolded protein response(UPR)along with the accumulation of protein aggregates.We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways,comprising adaptive UPR during pancreatic aging.Notably,we found aging-relatedβ-cell-specific upregulation of HSP90 B1,an endoplasmic reticulum-located chaperone,impeded high glucose-induced insulin secretion.Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis,suggesting an avenue to delayingβ-cell aging and preventing aging-related diabetes. | Jingyi Li Yuxuan Zheng Pengze Yan Moshi Song Si Wang Liang Sun Zunpeng Liu Shuai Ma Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Weiqi Zhang Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | National Science Review2021，8，2： | 3 |
| 6 | 不同物种端粒结合蛋白和端粒酶的研究进展显示文摘端粒位于真核生物染色体末端,在复制过程中保护染色体的完整性。端粒随着细胞的有丝分裂而缩短,端粒酶在胚胎干细胞等细胞中起到了延长端粒的作用。端粒结合蛋白包括shelterin复合体和CST复合体,端粒酶以自身RNA组分为模板逆转录合成端粒,端粒结合蛋白和端粒酶在保持端粒长度和稳定中都有重要作用。尽管不同物种中端粒序列类似,但是端粒及端粒酶在生理和/或病理状态下的功能却不尽相关。本文对不同物种的端粒结合蛋白和端粒酶的组成、功能等进行综述,以深入了解端粒生物学功能,为端粒功能障碍相关疾病的治疗提供科学基础。 | 石桂英 黄艺滢 雷雪裴 李欣悦 白琳 | 2022 | 中国比较医学杂志2022，32，3： | 1 |
| 7 | 合成盐酸中酸性废水的综合治理显示文摘对合成盐酸中的酸性废水循环利用 ,并用此酸性水作为生产普通盐酸的吸收水。实践证明 ,该方法是一种行之有效的治理途径 。 | 于德著 李苏峰 | 2000 | 江苏环境科技2000，13，1： | 1 |
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