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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

Protein & cell 2024年第6期15卷 441-459页

作者： Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu Guang-Hui Liu State Key laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine Department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China State Key laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China National laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS Key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint ***,the mechanism underlying human synovial aging remains poorly ***,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged *** delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged ***,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue *** particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged *** human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged *** data indicate an important role of FOXO1 in the regulation of human synovial ***,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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MAD2L2 overexpression attenuates the effects of TNF-α-induced migration and invasion capabilities in colorectal cancer cells

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BIOcell 2024年第9期48卷 1311-1322页

作者： HAOTONG SUN HEYING WANG YANJIE HAO XIN LI JUN LING HUAN WANG FEIMIAO WANG FANG XU School of Basic Medicine Medical Genetics and Cell BiologyNingxia Medical UniversityYinchuan750004China Key laboratory of Reproduction and Genetics Ningxia Medical UniversityYinchuan750004China

Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still ***:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory *** assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling *** sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor *** of MAD2L2 expression was facilitated via lentiviral vector-mediated *** influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then ***:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-α***,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and ***:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma ***,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.

关键词： Colorectal cancer TNF-α MAD2L2 Migration Invasion

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Skeletal stem cells in bone development,homeostasis,and disease

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Protein & cell 2024年第8期15卷 559-574页

作者： Guixin Yuan Xixi Lin Ying Liu Matthew B.Greenblatt Ren Xu The First Affliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal stem cell State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361005China Xiamen Key laboratory of Regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue RegenerationOrgan Transplantation InstituteSchool of MedicineXiamen UniversityXiamen 361102China Department of Pathology and laboratory Medicine Weill Cormell Medical CollegeNew YorkNY 10065USA Research Division Hospital for Special SurgeryNew YorkNY10065USA

Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem *** studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and *** investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time ***,recent studies have shed light on the characteristics of ssCs in both physiological and pathological *** review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

关键词： skeletal stem cells bone development endochondral ossification intramembranous ossification lineage tracing

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A Novel Poly(3-hexylthiophene) Engineered Interface for Electrochemical Monitoring of Ascorbic Acid During the Occurrence of Glutamate-Induced Brain Cytotoxic Edemas

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Research 2024年第1期2023卷 301-313页

作者： Zexuan Meng Yuchan Zhang Lu Yang Shuang Zhao Qiang Zhou Jiajia Chen Jiuxi Sui Jian Wang Lizhong Guo Luyue Chang Jialing He Guixue Wang Guangchao Zang Institute of Life Science and Laboratory of Tissue and Cell BiologyLab Teaching and Management CenterChongqing Medical UniversityChongqing 400016China Key laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China Jinfeng laboratory Chongqing 401329China Department of Pathophysiology Chongqing Medical UniversityChongqingChina

Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety *** this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)*** microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical ***,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA *** also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA *** study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the *** work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.

关键词： release microelectrode Engine

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RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key laboratory of Molecular Design for Plant cell Factory of Guangdong Higher Education Institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell *** these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling ***,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely ***,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling ***1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its ***,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl *** darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome *** findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein

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An effective pharmacological hydrogel induces optic nerve repair and improves visual function

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Science China(Life Sciences) 2024年第3期67卷 529-542页

作者： Lipeng Wang Shan Zhang Yawen Han Shuo Tang Jiarui Li Lina Bu Dongyu Zhao Hongkui Deng Department of cell biology Schoolof Basic Medical SciencesPeking University Stem Cell Research CenterStateKey Laboratoryof Naturaland Biomimetic DrugsPeking University Health Science Center Beijing 100191China MOE Key laboratory of cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Changping laboratory Beijing 102206China Department of Ophthalmology Peking University People's Hospital Eye Diseases and Optometry InstituteBeijing 100871China Department of Biomedical Informatics School of Basic Medical SciencesPeking UniversityBeijing 100191China

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

关键词： retinal ganglion cell axon regeneration old-age glaucoma small molecules pharmacological hydrogel visual function repair

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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China laboratory of Developmental biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(Pcells(Pcell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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乳酸化修饰参与调控DNA损伤修复和癌细胞化疗敏感性

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Science Bulletin 2024年第9期69卷 1185-1187页

作者：刘子超黄奕乐刘兴国 CAS Key laboratory of Regenerative biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong 999077China Guangdong Provincial Key laboratory of stem cell and Regenerative Medicine Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China University of Chinese Academy of Sciences Beijing 100049China

The phenomenon in which cells prefer glycolysis to oxidative phosphorylation with increased lactate production is known as the Warburg effect and is found prevalent in cancer cells and pluripotent stem cells [1]. In addition to being an intermediate metabolite of glycolysis, lactate has been reported as a signal involved in multiple important biological processes, such as innate immunity [2], the cell cycle [3], hippocampal neurogenesis [4].

关键词：化疗敏感性 immunity DNA损伤修复

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MSC-mediated mitochondrial transfer restores mitochondrial DNA and function in neural progenitor cells of Leber’s hereditary optic neuropathy

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Science China Life Sciences 2024年

作者： Rui Wang Feixiang Bao Manjiao Lu Xiaoyun Jia Jiahui Xiao Yi Wu Qingjiong Zhang Xingguo Liu Joint School of Life Sciences Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical University Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of Sciences Guangdong Provincial Key laboratory of stem cell and Regenerative Medicine CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences University of Chinese Academy of Sciences State Key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual Science

Leber’s hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA(mtDNA).Unfortunately,the available treatment options for LHON patients are limited due to challenges in mitochondrial *** our study,we reprogramming LHON urine cells into induced pluripotent stem cells (iPSCs) and differentiating them into neural progenitor cells (NPCs) and neurons for disease *** research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function,confirming the disease ***,through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells (MSCs),we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON *** findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs,even after their differentiation into *** discovery holds promise as a potential therapeutic strategy for LHON patients.

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Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural Regeneration Research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad Center of Regeneration Medicine and stem cell Research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during *** cells are generated in an organized fashion during *** early stages of brain development,neural stem cells(NSC... 详细信息

关键词： cortex cerebral development

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