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human pluripotent stem cell-derived kidney organoids:Current progress and challenges

World Journal of stem cells 2024年第2期16卷 114-125页

作者： Hong-Yan Long Zu-Ping Qian Qin Lan Yong-Jie Xu Jing-Jing Da Fu-Xun Yu Yan Zha Graduate School Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Laboratory Medicine Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Department of Nephrology Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Key Laboratory of Diagnosis and Treatment of Pulmonary Immune Diseases National Health CommissionGuizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal ***,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary ***,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug *** this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease ***,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

关键词： Kidney Organoids human pluripotent stem cell Development Vascular system Disease modeling

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An efficient protocol for studying human pluripotent stem cell-derived myotube senescence

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Biophysics Reports 2023年第5期9卷 232-240页

作者： Qian Zhao Ying Jing Shuai Ma Weiqi Zhang Jing Qu Si Wang Guang-Hui Liu State Key Laboratory of stem cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Advanced Innovation Center for human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Aging Translational Medicine Center International Center for Aging and Cancer Beijing Municipal Geriatric Medical Research Center Xuanwu Hospital Capital Medical University State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Beijing Institute for stem cell and Regenerative Medicine Institute for stem cell and Regeneration CAS University of Chinese Academy of Sciences CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics and China National Center for Bioinformation Chinese Academy of Sciences Sino-Danish College University of Chinese Academy of Sciences Sino-Danish Center for Education and Research

Sarcopenia, an age-related skeletal muscle condition characterized by a progressive decline in muscle mass and function, is linked to increased vulnerability, a higher likelihood of falls, and higher mortality rates in older individuals. A comprehensive understanding of the intricate mechanisms driving skeletal muscle aging is of great significance in both scientific and clinical fields. Consequently, myotube models that facilitate studying regulatory mechanisms underlying skeletal muscle aging are important tools required to advance intervention strategies against skeletal muscle aging and associated ***, we provide a detailed protocol to generate human pluripotent stem cells-derived myotubes and describe their applications in aging studies, as well as a troubleshooting for potential problems. Overall,this protocol serves as a valuable methodological reference for exploring the role and mechanism of genes involved in skeletal muscle aging.

关键词： human pluripotent stem cell Myotube Senescence Differentiation In vitro

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Transcriptomic Profiling of human pluripotent stem cell-derived Retinal Pigment Epithelium over Time

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Genomics, Proteomics & Bioinformatics 2021年第2期19卷 223-242页

作者： Grace E.Lidgerwood Anne Senabouth Casey J.A.Smith-Anttila Vikkitharan Gnanasambandapillai Dominik C.Kaczorowski Daniela Amann-Zalcenstein Erica L.Fletcher Shalin H.Naik Alex W.Hewitt Joseph E.Powell Alice Pebay Department of Anatomy and Neuroscience The University of MelbourneParkvilleVIC 3010Australia Department of Surgery The University of MelbourneParkvilleVIC 3010Australia Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC 3002Australia Garvan Weizmann Centre for cellular Genomics Garvan Institute of Medical ResearchThe Kinghorn Cancer CentreDarlinghurstNSW 2010Australia Single cell Open Research Endeavour The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Immunology Division The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical Biology The University of MelbourneParkvilleVIC 3010Australia School of Medicine Menzies Institute for Medical ResearchUniversity of TasmaniaHobartTAS 7005Australia UNSW cellular Genomics Futures Institute School of Medical SciencesUniversity of New South WalesSydneyNSW 2052Australia

human pluripotent stem cell(h PSC)-derived progenies are immature versions of cells,presenting a potential limitation to the accurate modelling of diseases associated with maturity or ***,it is important to characterise how closely cells used in culture resemble their native *** order to select appropriate time points of retinal pigment epithelium(RPE)cultures that reflect native counterparts,we characterised the transcriptomic profiles of the h PSC-derived RPE cells from 1-and 12-month *** differentiated the human embryonic stem cell line H9 into RPE cells,performed single-cell RNA-sequencing of a total of 16,576 cells to assess themolecular changes of the RPE cells across these two culture time *** results indicate the stability of the RPE transcriptomic signature,with no evidence of an epithelial–mesenchymal transition,and with the maturing populations of the RPE observed with time in *** of Gene Ontology pathways revealed that as the cultures age,RPE cells upregulate expression of genes involved in metal binding and antioxidant *** might reflect an increased ability to handle oxidative stress as cells *** with native human RPE data confirms a maturing transcriptional profile of RPE cells in *** results suggest that long-term in vitro culture of RPE cells allows the modelling of specific phenotypes observed in native mature *** work highlights the transcriptional landscape of h PSC-derived RPE cells as they age in culture,which provides a reference for native and patient samples to be benchmarked against.

关键词： human embryonic stem cell human pluripotent stem cell Retinal pigment epithelium Single-cell RNA sequencing Ageing

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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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Advances and Applications of Brain Organoids

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Neuroscience Bulletin 2023年第11期39卷 1703-1716页

作者： Yang Li Peng‑Ming Zeng Jian Wu Zhen‑Ge Luo School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

Understanding the fundamental processes of human brain development and diseases is of great importance for our ***,existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with *** the past years,an emerging model,the“brain organoid”integrated from human pluripotent stem cells,has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent,making it possible to better understand the complex structures and functions of the human *** this review,we summarize recent advances in brain organoid technologies and their applications in brain development and diseases,including neurodevelopmental,neurodegenerative,psychiatric diseases,and brain ***,we also discuss current limitations and the potential of brain organoids.

关键词： human pluripotent stem cell Brain organoid Brain development Neurological disease

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Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2

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Protein & cell 2021年第8期12卷 639-652页

作者： Xiaoying Chen Xu Han Bruno Bianchi Wuqiang Guan Weihong Ge Yong-Chun Yu Yi E.Sun Shanghai Institute of stem cell Research and Clinical Translation Shanghai East HospitalTongji University School of MedicineShanghai 200120China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceJing’an District Centre Hospital of ShanghaiFudan UniversityShanghai 200032China Department of Psychiatry and Biobehavioral Sciences David Geffen School of MedicineUCLALos AngelesCA 90095USA

Rett syndrome(RTT)is a progressive neurodevelop-mental disorder,mainly caused by mutations in MeCP2 and currently with no *** report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine ***,RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain *** of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons,which appeared to retain partial ***,consistent deficits in nuclear size,dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived *** neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2,strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the *** findings thus reveal stable neuronal maturation deficits and unexpectedly,graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency,which is informative for future therapeutic development.

关键词： MeCP2 Rett Syndrome human pluripotent stem cell neural differentiation

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