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2024年3月7日,Wiley旗下top期刊《AGING CELL》在线发表了云南师范大学生命科学学院郭锡汉副教授、汪旭教授课题组最新研究成果《Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner》。云南师范大学生命科学学院郭锡汉副教授、汪旭教授为共同通讯作者。
Abstract
Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age- and sex-related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild-type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6- to 14-month-old mice. Variation in TL was attributable to tissue type, age, genotype and, to a lesser extent, sex. Compared to WT, APP/PS1 had a significantly shorter baseline TL across all examined tissues. TL was inversely associated with age in both genotypes and TL shortening was accelerated in brain of APP/PS1. Age-related increase of micronuclei was observed in both genotypes but was accelerated in APP/PS1. We integrated TL and micronuclei data with data on cognition performance and brain amyloidosis. TL and micronuclei were linearly correlated with cognition performance or Aβ40 and Aβ42 levels in both genotypes but to a greater extent in APP/PS1. These associations in APP/PS1 mice were dominantly driven by females. Together, our findings provide foundational knowledge to infer the TL and micronuclei trajectories in APP/PS1 mice during disease progression, and strongly support that TL attrition and micronucleation are tightly associated with AD pathogenesis in a female-
扩展阅读:
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云南师范大学生命科学学院研究生导师简况表
郭锡汉 遗传学,博士,硕士生导师。 2011于云南师范大学获理学学士学位, 2014年获理学硕士学位, 2017于云南大学获理学博士学位。 主要招生专业: 生物与医药、食品加工与安全、遗传学 主要研究方向: 人类遗传学、医学遗传学、遗传毒理学、营养基因组学 |
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主要研究领域 微核(Micronucleus)的起源、命运及其病理/生理结果,包括PS1突变诱发阿尔兹海默病的机制研究、Y染色体丢失的诱因及其生理/病理学影响的研究、微营养物质对人类基因组稳定性的维护作用、药食两用植物化合物对人基因组稳定性的影响及其机制探究。累计主持国家自然科学基金2项,省部级基础科学研究计划2项。以第一作者或通讯作者在Aging Research Reviews、Human Genetics、International Journal of Cancer、Mutation Research Reviews、浙江大学学报(医学版)等国内外学术期刊发表学术论文20余篇。2019年获评云南师范大学优秀青年学者, 2021年获云南省自然科学二等奖(排名第3)。
学术任职及兼职: 2022.08-至今,任Frontiers in Aging杂志Genetics, Genomics and Epigenomics of Aging版块的副主编(Associate Editor)
近三年代表论文和奖励: *:通讯作者 (1) Xihan Guo*, Henning Hintzsche*, Weijiang Xu, Juan Ni, Jinglun Xue, Xu Wang*. Interplay of cGAS with micronuclei: regulation and diseases. Mutation Research/Reviews in Mutation Research, 2022, 790: 108440. (2) Ting Lyu, Hongyuan Zhou, Yihui Wang, Minyan Jiang, Qian Tao, Juanlin Chen, Yitong Guo, Qiuping Zhang, Xu Wang, Xihan Guo*. High-dose metformin induces a low-glucose dependent genotoxic stress. Food and Chemical Toxicology, 2022, 165: 113129. (3) 张城,汪旭,郭锡汉*,免疫原性微核的起源与生物医学意义,生命科学,2022, 34: 392-400. (4) Jianfei Li, Cheng Zhang, Lingzhi Li, Xueqin Hu, Yizhen Jia, Yanan Huang, Ting Lyu, Xu Wang, Xihan Guo*. Folate deficiency enhances the in vitro genotoxicity of bile acids in human colon and liver cells. Mutagenesis, 2022, 37: 34-43. (5) Xihan Guo*. Loss of Y chromosome at the interface between aging and Alzheimer’s disease. Cellular and Molecular Life Sciences, 2021, 78 (21), 7081-7084. (6) Xihan Guo*, Yanmei Qi, Jianfei Li, Houhong Fan, Limei Yang, Xue Wu, Juan Ni, Han Wang, Xu Wang*. A comprehensive study of the genotoxic and anti-genotoxic effects of homocysteine in HUVECs and mouse bone marrow cells. Food and Chemical Toxicology, 2021, 156: 112518. (7) Xihan Guo*, Jianfei Li, Jinglun Xue, Michael Fenech*, Xu Wang*. Loss of Y chromosome: An emerging next-generation biomarker for disease prediction and early detection? Mutation Research/Reviews in Mutation Research, 2021, 788: 108389. (8) Xueqin Dai, Xihan Guo*. Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations Ageing Research Reviews, 2021, 68: 101342. (9) Xihan Guo, Xueqin Dai, Xue Wu, Neng Cao, Xu Wang*. Small but strong: Mutational and functional landscapes of micronuclei in cancer genomes. International Journal of Cancer, 2021, 148(4): 812-824. (10) Xihan Guo, Chunlei Wang, Weimeng Tian, Xueqin Dai, Juan Ni, Xiayu Wu, Xu Wang*. Extract of bulbus of Fritillaria cirrhosa induces spindle multipolarity in human-derived colonic epithelial NCM460 cells through promoting centrosome fragmentation. Mutagenesis, 2021, 36 (1): 95-107. (11) Ling Yan, Ziru Zhao, Xiaoran Wang, Ting Lyu, Jianfei Li, Yanmei Qi, Xu Wang, Xihan Guo*. Short-term in vitro glutamine restriction differentially impacts the chromosomal stability of transformed and non-transformed cells. Mutagenesis, 2020, 35 (5): 425-435 (12) 严敏、汪旭、郭锡汉*. 早老蛋白 1 功能缺失性突变导致家族性阿尔茨海默病的研究进展. 浙江大学学报(医学版),2020,49 (4): 487-499. (13) Xihan Guo, Xueqin Dai, Xue Wu, Tao Zhou, Juan Ni, Jinglun Xue, Xu Wang*. Understanding the birth of rupture-prone and irreparable micronuclei. Chromosoma, 2020,129 (3): 181-200. (14) Xihan Guo, Xueqin Dai, Tao Zhou, Han Wang, Juan Ni, Jinglun Xue, Xu Wang*. Mosaic loss of human Y chromosome: what, how and why. Human Genetics, 2020, 139 (4), 421-446. (15) Xihan Guo, Xiayu Wu, Juan Ni, Ling Zhang, Jinglun Xue, Xu Wang*. Aqueous extract of bulbus Fritillaria cirrhosa induces cytokinesis failure by blocking furrow ingression in human colon epithelial NCM460 cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2020, 850: 503147. (16) Xihan Guo, Xueqin Dai, Juan Ni, Xiaoling Ma, Jinglun Xue, Xu Wang*. Geraniin differentially modulates chromosome stability of colon cancer and noncancerous cells by oppositely regulating their spindle assembly checkpoint. Environmental and molecular mutagenesis, 2019, 60(3), 254-268. (17) Xihan Guo, Xueqin Dai, Juan Ni, Neng Cao, Guofang Yang, Jinglun Xue, Xu Wang*. High concentration of sugars is genotoxic to folate-deficient cells. Mutation Research/Fundamental and Molecular mechanisms of Mutagenesis, 2019, 814, 15-22. (18) Xihan Guo, Juan Ni, Ziqing Liang, Jinglun Xue, Michael F Fenech, Xu Wang*. The molecular origins and pathophysiological consequences of micronuclei: New insights into an age-old problem. Mutation Research/Reviews in Mutation Research, 2019, 779, 1-35. (19) 汪旭,倪娟,郭锡汉,王晗,周滔,2021年云南省自然科学二等奖
近三年主持的国家级和省部级科研项目: 1. 国家自然科学基金青年基金.免疫原性微核激活cGAS-STING通路并影响PS1突变诱导Aβ形成的机制研究,25万,2020.01–2022.12. 2. 国家自然科学基金地区基金.利用小鼠模型研究Y染色体丢失对阿尔茨海默病的影响及分子机制,33万,2023.01-2026.12. 3. 云南省基础研究计划青年项目,PS1突变通过激活L1逆转录转座子诱导人神经细胞固有免疫的机制研究,5万,2020.06–2023.05. 4. 云南省基础研究计划面上项目,免疫原性微核介导的cGAS-STING-IRF3信号轴在二甲双胍抗癌活性中的作用探究,10万,2021.04–2024.03.
近三年主讲课程(研究生,本科): 硕士生课程:现代生物技术研究方法。 本科生课程:分子生物学、遗传学、生物科学专业英语、看得见的基因、环境-遗传互作与健康结局分析技术。 |
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