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One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina Institute for stem cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina National stem cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing Institute for stem cell and Regenerative Medicine BeijingChina State Key laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

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Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： Fei Teng Tongtong Cui Li Zhou Qingqin Gao Qi Zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key laboratory of stem cell and Regenerative biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China

cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat ***,concerns over the safety and efficacy require to be further addressed in order to realize their full *** receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful *** designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or *** review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical *** a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic ***,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

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Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key laboratory of Regenerative biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou Regenerative Medicine and Health Guang Dong laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

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The evolving views of hematopoiesis:from embryo to adulthood and from in vivo to in vitro

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Journal of Genetics and Genomics 2024年第1期51卷 3-15页

作者： Yifan Zhang Feng Liu Shandong Provincial Key laboratory of Animal cell and Developmental biology School of Life SciencesShandong UniversityQingdaoShandong 266237China State Key laboratory of Membrane biology Institute of ZoologyInstitute for Stem Cell and RegenerationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China

The hematopoietic system composed of hematopoietic stem and progenitor cells(HSPCs)and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate *** gastrulation onwards,there successively emerge primitive hematopoiesis(that produces specialized he-matopoietic cells),pro-definitive hematopoiesis(that produces lineage-restricted progenitor cells),and definitive hematopoiesis(that produces multipotent HSPCs).These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic *** development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental *** to the progressive methodology(e.g.,high-throughput lineage tracing and single-cell functional and omics analyses),our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated;meanwhile,new paradigms to characterize rare cell types,cell heterogeneity and its causes,and comprehensive regulatory landscapes have been ***,we review the evolving views of HSPC biology during developmental and postnatal ***,we discuss recent advances in the in vitro induction and expansion of HSPCs,with a focus on the implications for clinical applications.

关键词： Hematopoietic stem and progenitor cell Developmental hematopoiesis Postnatal hematopoiesis In vitro hematopoiesis

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Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

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Neural Regeneration Research 2024年第4期19卷 711-712页

作者： Masakazu Iwamoto Taito Matsuda Department of stem cell biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous *** adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

关键词： neural integrate continuously

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OIP5 Interacts with NCK2 to Mediate Human Spermatogonial stem cell Self-Renewal and Apoptosis through cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The Key laboratory of Model Animals and stem cell biology in Hunan Province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative ***,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain ***,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human *** sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown ***2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their ***,NCK2 knockdown reversed the influence of OIP5 overexpression on human ***,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably ***,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile ***,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with *** such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

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Temporal and spatial regulation of biomimetic vascularization in 3D-printed skeletal muscles

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Bio-Design and Manufacturing 2024年第5期7卷 597-610页

作者： Minxuan Jia Tingting Fan Tan Jia Xin Liu Heng Liu Qi Gu Key laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Membrane BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Orthopaedics Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and *** study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle *** harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent *** findings highlight the importance of the interaction dynamics between these two cell ***,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube ***,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle *** methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal ***,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial *** on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.

关键词： Skeletal muscle Vascularization 3D bioprinting cell interaction

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Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： Shan Zhang Ayao Guo Huan Wang Jia Liu Chenshuang Dong Junyi Ren Guiling Wang Key laboratory of cell biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China Department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear *** evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor *** present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target *** systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： Cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

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Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

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Zoological Research 2024年第2期45卷 242-252页

作者： Xiu-Sheng Chen Rui Han Yan-Ting Liu Wei Huang Qi Wang Xin Xiong Ying Zhang Jian-Guo Zhao Shi-Hua Li Xiao-Jiang Li Wei-Li Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State Key laboratory of stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against *** in PINK1 and Parkin can lead to loss of function and early onset Parkinson's ***,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces ***,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit *** our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent *** extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig *** contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig *** of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey ***,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and *** findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

关键词： PINK1 Parkin Mitochondria Phosphorylation Non-human primates Pigs

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Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

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Journal of Molecular cell biology 2024年第1期16卷 15-28页

作者： Te Li Min Liu Fan Yu Song Yang Weiwen Bu Kai Liu Jia Yang Hua Ni Mulin Yang Hanxiao Yin Renjie Hong Dengwen Li Huĳie Zhao Jun Zhou Haihe laboratory of cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China laboratory of Tissue Homeostasis Haihe Laboratory of Cell EcosystemTianjin 300462China Center for cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongShandong Provincial Key Laboratory of Animal Resistance BiologyCollege of Life SciencesShandong Normal UniversityJinan 250014China

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan ***,the mechanistic link of cilia to CMD complications is still poorly ***,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar ***,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl *** studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium *** vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm *** findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

关键词： carbohydrate metabolism disorder aldose aldehyde cilium disassembly formyl group calcium influx HDAC6

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