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cellular & Molecular Immunology 2021年第9期18卷 2224-2235页

作者： Zongshan Shen Shuhong Kuang Min Zhang Xin Huang Jiayao Chen Meiliang Guan Wei Qin Hockin H.K.Xu Zhengmei Lin Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhouGuangdongChina department of Andrology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina The Key Laboratory for stem cells and Tissue Engineering Center for Stem Cell Biology and Tissue EngineeringMinistry of EducationSun Yat-sen UniversityGuangzhouGuangdongChina department of Advanced Oral Sciences&Therapeutics University of Maryland School of DentistryBaltimoreMDUSA center for stem cell biology and Regenerative Medicine University of Maryland School of MedicineBaltimoreMDUSA University of Maryland Marlene and Stewart Greenebaum Cancer center University of Maryland School of MedicineBaltimoreMDUSA

Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from *** is caused by diabetes-enhanced host immune-inflammatory responses to bacterial *** this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to ***,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal ***,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic *** finding provides a basis for the development of an effective therapeutic approach for treating DP.

关键词： Diabetes-associated periodontitis bindarit proinflammatory monocytes macrophages

Myogenesis controlled by a long non-coding RNA 1700113A16RIK and post-transcriptional regulation

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cell Regeneration 2022年第1期11卷 120-130页

作者： Xin Fu Sheng Li Minzhi Jia Bo Xu Lele Yang Ruimiao Ma Hong Cheng Wenjun Yang Ping Hu Spine center Department of Pediatric OrthopedicsXin Hua Hospital Affiliated to Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200092China State Key Laboratory of cell biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China Guangzhou Laboratory Guangzhou 510700GuangdongChina State Key Laboratory of Molecular biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Long non-coding(lnc)RNA plays important roles in many cellular *** function of the vast majority of lncRNAs remains *** we identified that lncRNA-1700113A16RIK existed in skeletal muscle stem cells(MuSCs)and was significantly elevated during MuSC *** of 1700113A16RIK inhibits the differentiation of muscle stem *** contrast,overexpression of 1700113A16RIK promotes the differentiation of muscle stem *** study shows the muscle specific transcription factor Myogenin(MyoG)positively regulates the expression of 1700113A16RIK by binding to the promoter region of ***,1700113A16RIK may regulate the expression of myogenic genes by directly binding to 3’UTR of an important myogenic transcription factor MEF2D,which in turn promotes the translation of *** together,our results defined 1700113A16RIK as a positive regulator of MuSC differentiation and elucidated a mechanism as to how 1700113A16RIK regulated MuSC differentiation.

关键词： Long non-coding RNA(lncRNA) 1700113A16RIK Muscle stem cell(MuSC)differentiation Myocyte-specific enhancer binding factor 2(MEF2D)

BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period

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Protein & cell 2024年第1期15卷 21-35页

作者： Zhenmeiyu Li Guoping Liu Lin Yang Mengge Sun Zhuangzhi Zhang Zhejun Xu Yanjing Gao Xin Jiang Zihao Su Xiaosu Li Zhengang Yang State Key Laboratory of Medical Neurobiology and MOE Frontiers center for Brain Science Institutes of Brain Scienceand Department of NeurologyZhongshan HospitalFudan UniversityShanghai 200433China

The seat of human intelligence is the human cerebral cortex,which is responsible for our exceptional cognitive *** principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so *** remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells,primary neural stem cells in the cortex,generate cortical pyramidal neurons for more than 130 days,whereas the same process takes only about 7 days in *** molecular mechanisms underlying this difference are largely ***,we found that bone morphogenic protein 7(BMP7)is expressed by increasing the number of corti-cal radial glial cells during mammalian evolution(mouse,ferret,monkey,and human).BMP7 expression in cortical radial glial cells promotes neurogenesis,inhibits gliogenesis,and thereby increases the length of the neurogenic period,whereas Sonic Hedgehog(SHH)signaling promotes cortical *** demonstrate that BMP7 sign-aling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor *** propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.

关键词： radial glia cortical neurogenesis cortical gliogenesis cortical evolution BMP7 SHH

Systematic Exploration of Optimized Base Editing gRNA Design and Pleiotropic Effects with BExplorer

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Genomics, Proteomics & Bioinformatics 2023年第6期21卷 1237-1245页

作者： Gongchen Zhang Chenyu Zhu Xiaohan Chen Jifang Yan Dongyu Xue Zixuan Wei Guohui Chuai Qi Liu Translational Medical center for stem cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Base editing technology is being increasingly applied in genome engineering,but the current strategy for designing guide RNAs(gRNAs)relies substantially on empirical experience rather than a dependable and efficient in silico ***,the pleiotropic effect of base editing on disease treatment remains unexplored,which prevents its further clinical ***,we presented BExplorer,an integrated and comprehensive computational pipeline to optimize the design of gRNAs for 26 existing types of base editors in *** BExplorer,we described its results for two types of mainstream base editors,BE3 and ABE7.10,and evaluated the pleiotropic effects of the corresponding base editing *** revealed 524 and 900 editable pathogenic single nucleotide polymorphism(SNP)loci in the human genome together with the selected optimized gRNAs for BE3 and ABE7.10,*** addition,the impact of 707 edited pathogenic SNP loci following base editing on 131 diseases was systematically explored by revealing their pleiotropic effects,indicating that base editing should be carefully utilized given the potential pleiotropic ***,the systematic exploration of optimized base editing gRNA design and the corresponding pleiotropic effects with BExplorer provides a computational basis for applying base editing in disease treatment.

关键词： Gene editing Base editing Pleiotropy CRISPR/Cas9 gRNAdesign

An overview of autophagy in the differentiation of dental stem cells

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BIOcell 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU LULU WANG LI-AN WU State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.

关键词： Dental stem cells cell differentiation Autophagy Mitophagy Autophagy regulation

Proliferation and differentiation into endothelial cells of human bone marrow mesenchymal stem cells (MSCs) on poly DL-lactic-co-glycolic acid (PLGA) films

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Chinese Science Bulletin 2006年第11期51卷 1328-1333页

作者： YUE Huimin ZHANG Lei WANG Yunfang LIANG Feng GUAN Lidong Li Shaoqing YAN Fang NAN Xue BAI Cixian LIN Feng YAN Yongnian PEI Xuetao department of stem cell biology Institute of Transfusion Medicine Academy of Military Medical Sciences Beijing 100850 China Research center of Laser Rapid Forming Mechanical Department of Tsinghua University Beijing 100084 China These authors contributed equally to this work.

The functional realization is the most important problem in vascular tissue engineering. The small-caliber blood vessel substitutes are prone to thrombi, which results in functional loss of blood vessels. However, this is probably due to the imper- fection of endothelial layer in the substitutes. In this study, MSCs were seeded on a series of porous PLGA films with various porosity and pore size made by sodium chloride (NaCl) particulate leaching, and cell proliferation on each film was inspected. The film made of the 75% (w/w) particulate proportion and 30―50 μm pore size maximized the proliferation rate and was chosen as the scaffolds for the differentia- tion of MSCs into endothelial cells. The induced cells expressed endothelial cells specific Flk-1, Ⅷ factor and CD34, possessed endothelial cells specific Weible-palade (W-P) body, and had the abilities of ingesting low density lipoprotein and secreting prostacyclin (PGI2). The results show that MSCs not only have the ideal biological compatibility with the porous PLGA films, but also have the potency of dif- ferentiating into functional endothelial cells, whichshould facilitate the endothelialization in vascular tissue engineering.

关键词： MSCs PLGA 内皮细胞内皮化维管组织工程

Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation

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骨研究:英文版 2023年第3期11卷 560-573页

作者： Ruici Yang Dandan Cao Jinlong Suo Lingli Zhang Chunyang Mo Miaomiao Wang Ningning Niu Rui Yue Weiguo Zou State Key Laboratory of cell biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Shenzhen Institute of Synthetic biology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China

A distinct population of skeletal stem/progenitor cells(SSPCs)has been identified that is indispensable for the maintenance and remodeling of the adult ***,the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be ***,we established models of premature aging by conditional depletion of Zmpste24(Z24)in mice and found that Prx1-dependent Z24 deletion,but not Osx-dependent Z24 deletion,caused significant bone ***,Acan-associated Z24 depletion caused only trabecular bone ***-cell RNA sequencing(sc RNA-seq)revealed that two populations of SSPCs,one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells,were significantly decreased in Prx1-Cre;Z24^(f/f)*** premature SSPC populations exhibited apoptotic signaling pathway activation and decreased *** exercise reversed the effects of Z24depletion on cellular apoptosis,extracellular matrix expression and bone *** study identified two populations of SSPCs that are responsible for premature aging-related bone *** impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.

关键词： sensation progenitor mec

Mitochondria-mediated apoptosis in mammals

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Protein & cell 2014年第10期5卷 737-749页

作者： Shunbin Xiong Tianyang Mu Guowen Wang Xuejun Jiang department of Genetics The University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Institute of Cancer stem cell Dalian Medical University Cancer Center 9 Lvshun Road South Dalian 116044 China department of Bone and Soft Tissue Tumors Tianjin Medical University Cancer Institute & Hospital Tianjin 300060 China cell biology Program Memorial SIoan-Kettering Cancer Center New York NY 10065 USA

The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization （MOMP） and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, main- tenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehen- sively studied, yet a great deal of new evidence indi- cates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the tar- geted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications.

关键词： apoptosome Bcl-2 family lAPs lAPantagonists cancer therapy

Structural basis of heparan sulfate-specific degradation by heparinase Ⅲ

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Protein & cell 2012年第12期3卷 950-961页

作者： Wei Dong Weiqin Lu Wallace L.McKeehan Yongde Luo Sheng Ye Life Sciences Institute Zhejiang UniversityHangzhou 310058China center for Cancer and stem cell biology Institute of Biosciences and TechnologyTexas A&M Health Science CenterHoustonTexas 77030USA department of Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTexas 77030USA

Heparinase Ⅲ(HepⅢ)is a 73-kDa polysaccharide lyase(PL)that degrades the heparan sulfate(HS)polysaccharides at sulfate-rare regions,which are important co-factors for a vast array of functional distinct proteins including the well-characterized antithrombin and the FGF/FGFR signal transduction *** functions in cleaving metazoan heparan sulfate(HS)and providing carbon,nitrogen and sulfate sources for host *** has long been used to deduce the structure of HS and heparin motifs;however,the structure of its own is *** we report the crystal structure of the HepⅢ from Bacteroides thetaiotaomicron at a resolution of 1.6Å.The overall architecture of HepⅢ belongs to the(α/α)5 toroid subclass with an N-terminal toroid-like domain and a C-terminal β-sandwich *** of this high-resolution structure allows us to identify a potential HS substrate binding site in a tunnel between the two domains.A tetrasaccharide substrate bound model suggests an elimination mechanism in the HS ***260 and His464 neutralize the carboxylic group,whereas Tyr314 serves both as a general base in C-5 proton abstraction,and a general acid in a proton donation to reconstitute the terminal hydroxyl group,*** structure of HepⅢ and the proposed reaction model provide a molecular basis for its potential practical utilization and the mechanism of its eliminative degradation for HS polysaccarides.

关键词： heparinaseⅢ crystal structure heparan sulfate fibroblast growth factor(FGF) β-elimination

New strategies for the repair of spinal cord injury

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Chinese Science Bulletin 2014年第31期59卷 4041-4049页

作者： Zhourui Wu Ziru Zhao Yan Yu Xiao Hu Wei Xu Zhili Zeng Yi Eve Sun Liming Cheng department of Spine Surgery Shanghai Tongji HospitalTongji University School of Medicine Translational stem cell center Shanghai Tongji HospitalTongji University School of Medicine

Spinal cord injury(SCI)leads to several neurologic damages to patients with sensory and motor function *** some inspiring results were reported in animal,even in non-human primate models,the clinical translation of these research achievements barely move forward for the SCI *** review mainly focused on the pathogenesis of the primary and secondary injury,the clinical therapies and the new technologies in spinal cord ***,the key scientific issues on this field were discussed in the ***,some suggestions were proposed for the scientific and clinical researches.

关键词：脊髓损伤修复临床治疗动物模型科学问题运动功能研究成果发病机制