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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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Foundation models in molecular biology

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Biophysics Reports 2024年第3期10卷 135-151页

作者： Yunda Si Jiawei Zou Yicheng Gao Guohui Chuai Qi Liu Luonan Chen Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai institute of Biochemistry and cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences translational medical center for stem cell therapy and institute for regenerative medicine Shanghai East Hospital Frontier Science Center for Stem Cell Research Bioinformatics Department School of Life Sciences and Technology Tongji University Shanghai Research institute for Intelligent Autonomous Systems

Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.

关键词： Foundation models Molecular biology Transcriptome

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Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin institutes of Health Science Tianjin 301600China CAMS center for stem cell medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

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Glial progenitor heterogeneity and plasticity in the adult spinal cord

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Neural Regeneration Research 2024年第12期19卷 2567-2568页

作者： Haichao Wei Jia Qian Wu Department of Neurosurgery McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTXUSA center for stem cell and regenerative medicine UT Brown Foundation Institute of Molecular MedicineHoustonTXUSA MD Anderson Cancer center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous *** progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific ***,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous *** development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.

关键词： functions plasticity thoroughly

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Ethical concerns in aging research:perspectives of global frontline researchers

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Science China(Life Sciences) 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv Guang-Hui Liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing institute for stem cell and regenerative medicine Beijing 100101China institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium(ABC) Beijing 100101China School of Life Science Beijing Institute of TechnologyBeijing 100081China School of Life Sciences Xiamen UniversityXiamen 361102China Advanced Innovation center for Human Brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Aging translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health *** global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging,a consensus regarding the feasibility of delaying aging,and multiple perspectives regarding lifespan *** present findings underscore a paradigm shift toward inclusive and ethically sound research,emphasizing the need for an approach that strikes a balance between basic and clinical *** addition,this study highlighted key ethical concerns in aging research,including the effects of misleading advertising,potential inequality in access to aging interventions,and risks pertaining to the extrapolation of research findings from lower-model organisms to *** insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu Guang-Hui Liu Advanced Innovation center for Human Brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital medical University Beijing 100053China 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 Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related ***,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ***,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche *** in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during *** particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular *** study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

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

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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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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging translational medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China institute for stem cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing institute for stem cell and regenerative medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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MAVS Antagonizes Human stem cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song Juan Carlos Izpisua Belimonte Jing Qu Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for stem cell and Regeneration Chinese Academy of Sciences Beijing 100101China Beijing institute for stem cell and regenerative medicine Bejing 100101China Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

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CD147 facilitates cisplatin resistance in ovarian cancer through FOXM1 degradation inhibition

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Genes & Diseases 2024年第5期11卷 122-125页

作者： Miao Wang Lin Chen Yu Wang Tian Fan Chunyu Zhu Zhixian Li Lei Mou Hong Yang Airong Qian Yu Li School of Life Sciences Northwestern Polytechnical UniversityXi’anShaanxi 710072China Xi’an Key Laboratory of stem cell and regenerative medicine Institute of Medical ResearchNorthwestern Polytechnical UniversityXi’anShaanxi 710072China Department of Oncology Air Force Medical CenterPLABeijing 100142China Department of Obstetrics and Gynecology The First Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi 710032China

Currently,the major therapy for patients with ovarian cancer includes post-cytoreductive surgery followed by chemotherapy of carboplatin or cisplatin plus *** rise of drug resistance is a substantial factor in cancer recurrence and mortality among ovarian cancer patients receiving cisplatin ***147 is widely expressed in a variety of cancer tissues1 and recognized as a drug target for its antibody drug Licartin which has been approved by China’s National medicines and Pharmaceutical Administration.2 Even though many studies reported that CD147 is involved in the cisplatin resistance of varieties of cancers,3 its mechanism remains *** this investigation,we uncovered a distinctive mechanism by which CD147 regulates cisplatin resistance through the proteasomal degradation of the transcription factor FOXM1,which is associated with DNA damage repair,in ovarian cancer *** results suggest that targeting CD147 may have therapeutic implications for increasing cisplatin efficiency in the management of ovarian cancer.

关键词： FOXM1 cisplatin CD147

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