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TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

Zoological Research 2024年第4期45卷 937-950页

作者： Yi-Fu Zhu Rong-Hua Yu Shuai Zhou Pei-Pei Tang Rui Zhang Yu-Xin Wu Ran Xu Jia-Ming Wei Ying-Ying Wang Jia-Li Zhang Meng-Ke Li Xiao-Jing Shi Yu-Wei Zhang Guang-Zhi Liu Rick FThorne Xu Dong Zhang Mian Wu Song Chen School of life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Translational Research Institute of Henan Provincial People’s Hospital and People'’s Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450053China Institute of Medicinal Biotechnology Jiangsu College of NursingHuai’anJiangsu 223300China Laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China Henan Key Laboratory of stem cell Differentiation and Modification Henan Provincial People’s HospitalHenan UniversityZhengzhouHenan 450053China School of Biomedical Sciences and Pharmacy The University of NewcastleNSW 2308Australia

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental *** highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained ***,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in *** deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse ***,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate ***,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this ***,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO ***,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

关键词： Non-canonical autophagy TAX1BP1 FIP200 p62 Aggregates Neural stem cell

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In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration Research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda Department of stem cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA stem cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International llc MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Hematopoietic aging:cellular,molecular,and related mechanisms

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Chinese Medical Journal 2024年第11期137卷 1303-1312页

作者： Li Ye Chuan Tian Ye Li Hang Pan Jinxiu Hu Liping Shu Xinghua Pan The stem cells and Immune cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan ProvinceKunming Key Laboratory of Stem Cell and Regenerative MedicineBasic Medical Laboratory920th Hospital of Joint Logistics Support ForcePLAKunmingYunnan 650032China Department of Immunology of School of Basic Medicine of Guizhou Medical University National and Local Joint Engineering Laboratory of Cell Engineering Biomedical TechnologyKey Laboratory of Regenerative Medicine of Guizhou ProvinceState Key Laboratory of Efficacy and Utilization of Medicinal Plants Co-constructed by Province and MinistryKey Laboratory of Translational Research of Adult Stem Cell of Chinese Academy of Medical SciencesGuiyangGuizhou 550025China

Aging is accompanied by significant inhibition of hematopoietic and immune system function and disruption of bone marrow ***-related alterations in the inflammatory response,immunity,and stem cell niches are at the root of hematopoietic *** the molecular mechanisms underlying hematopoietic and bone marrow aging can aid the clinical treatment of aging-related *** particular,it is unknown how the niche reprograms hematopoietic stem cells(HSCs)in an age-dependent manner to maintain normal hematopoiesis in elderly ***,specific inhibitors and blood exchange methods have been shown to reshape the hematopoietic niche and reverse hematopoietic ***,we present the latest scientific discoveries related to hematopoietic aging and hematopoietic system rejuvenation,discuss the relationships between hematopoietic niche aging and HSC aging,and describe related studies on stem cell-mediated regulation of hematopoietic aging,aiming to provide new ideas for further study.

关键词： stem cells Hematopoietic stem cell Niche Hematopoietic aging

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Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo stem cell Biology and Therapy Laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma stemness

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for stem cell Biology and Regenerative Medicine Stanford University School of MedicineStanford CA 94305USA Department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA Department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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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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Yap Controls Notochord Formation and Neural Tube Patterning by Integrating Mechanotransduction with FoxA2 and Shh Expression

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医用生物力学 2024年第S1期 604-604页

作者：程才奇 Yingzi Yang Department of Developmental Biology Harvard School of Dental MedicineHarvard Stem Cell Institute

目的正确的脊索和神经管(NT)形成对于中枢神经系统的发育至关重要。在胚胎发育中,生物力信息不断被胚胎细胞收集,生化和生物物理信号控制着胚胎的生长和模式化。然而,目前对生物信号的功能以及其与生物物理刺激是如何相互作用的仍知之...

目的正确的脊索和神经管(NT)形成对于中枢神经系统的发育至关重要。在胚胎发育中,生物力信息不断被胚胎细胞收集,生化和生物物理信号控制着胚胎的生长和模式化。然而,目前对生物信号的功能以及其与生物物理刺激是如何相互作用的仍知之甚少。方法本试验利用原子力显微镜量化神经管发育过程中的组织硬度,通过构建基质胶外植体培养体系、多种转基因小鼠模型、胚胎原位杂交技术、免疫荧光、萤光素酶报告基因检测等实验,探究Yap在神经形成中的作用。结果在胚胎形态发生过程中,脊索和神经管中存在机械应力和组织硬度梯度。脊索和神经管腹侧中最高的机械应力诱导Yap转录因子在脊索和底板中的激活,从而直接促进腹侧组织中心形成及其中Fox A2和Shh的表达。在底板中,Yap通过与Fox A2相互作用,是促进神经管中Shh表达的必要和充分条件。Hedgehog信号激活可挽救由Yap缺乏引起的神经管模式化缺陷,但不能挽救脊索形成,因此,Yap是独立于Hedgehog信号传导的脊索形成所必需的。结论胚胎形态发生过程中产生的生物物理刺激对包括神经管在内的中线结构的生长及形态范式发生起着指导作用,本研究揭示了Yap作为胚胎生长和编排的信号中心,将机械刺激转化为生化信号激活的一项极其重要的功能。

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RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

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Science China(life Sciences) 2024年第10期67卷 2186-2197页

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University&Institute of Cancer stem cell Dalian Medical UniversityDalian 116023China Department of Immunology College of Basic Medical SciencesDalian Medical UniversityDalian 116044China Institute of Cancer stem cell Dalian Medical UniversityDalian 116044China Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical UniversityDalian 116011China Department of General Surgery the Second Hospital of Hebei Medical UniversityShijiazhuang 050000China The Second Department of General Surgery the Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma Shijiazhuang 050001China

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis;however,their specific involvement in colon cancer remains largely *** we report that the splicing factor RBM25 is overexpressed in colon cancer,and this increased expression correlates with a poor prognosis of patients with colon ***,RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in ***,our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon ***,RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a,thereby inhibiting the selection of the proximal 3'splice site(ss),resulting in the production of the oncogenic short isoform,*** of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b ***,re-expression of MNK2b or blocking the 3′ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor ***,MNK2b levels were significantly increased in colon cancer tissues,which is positively correlated with the expression level of ***,our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer,suggesting its potential as a prognostic marker and therapeutic target.

关键词： RBM25 colon cancer alternative splicing MNK2

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Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

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Biomedical and Environmental Sciences 2024年第1期37卷 117-121页

作者： WEN Si Hui LI Lu Bei HUANG Hui Dan XIE Ying LUO Lei Key Laboratory of Molecular Epidemiology of Hunan Province School of MedicineHunan Normal UniversityChangsha 410081HunanChina Department of Occupational Health Changsha Centre for Disease Control and PreventionChangsha 410004HunanChina The Key Laboratory of Model Animals and stem cell Biology in Hunan Province Hunan Normal University School of MedicineChangsha 410013HunanChina

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

关键词： Renal kidney cadmium

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