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Comments on ‘Molecular architecture of lineage allocation and tissue organization in early mouse embryo’

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Journal of Molecular Cell Biology 2019年第11期11卷 1024-1025页

作者： Guizhong Cui naihe jing Guangdun Peng Guangzhou Regenerative Medicine and Health Guangdong Laboratory(GRMH-GDL) GuangzhouChina State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina Institute for Stem Cells and Regeneration Chinese Academy of SciencesBeijingChina

Single-cell RNA-seq,with its capability to align cells of continuously changed status by pseudo-time reconstruction,has greatly revolutionized the understanding of cell fate transition during embryo development(Shapir... 详细信息

关键词： al. continuously embryo

The promise of stem cells in the therapy of Alzheimer’s disease

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Translational Neurodegeneration 2015年第1期4卷 54-58页

作者： Chunmei Yue naihe jing State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

Alzheimer’s disease(AD),a common neurodegenerative disorder associated with gradually to dramatic neuronal death,synaptic loss and dementia,is considered to be one of the most obscure and intractable brain disorders in ***,there is no therapy clinically available to induce marked symptomatic relief in AD *** recent years,the proof-of-concept studies using stem cell-based approaches in transgenic AD animal models provide new hope to develop stem cell-based therapies for the effective treatment of *** degeneration of basal forebrain cholinergic neurons(BFCNs)and the resultant cholinergic abnormalities in the brain contribute substantially to the cognitive decline of AD *** approches using stem cell-derived BFCNs as donor cells need to be developed,and to provide proof of principle that this subtype-specific neurons can induce functional recovery of AD animal *** the continuous scientific advances in both academic and industrial fields,the potentials of stem cells in cellular neuroprotection and cell replacement in vivo have been elucidated,and stem cell-based therapy for repairing degenerative brains of AD is promising.

关键词： Alzheimer’s disease Stem cell-based therapy Basal forebrain cholinergic neurons Cognitive impairment,Embryonic stem cells

Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies

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National Science Review 2017年第4期4卷 533-542页

作者： Guangdun Peng Patrick P.L.Tam naihe jing State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of SciencesUniversity of Chinese Academy of Sciences Embryology Unit Children’s Medical Research Institute School of Medical SciencesSydney Medical School University of Sydney School of Life Science and Technology Shanghai Tech University

Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular *** recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular,population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.

关键词： early development cell lineage cell identity scRNA-seq spatial transcriptome

BMP signaling pathway and spinal cord development

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Frontiers in Biology 2012年第1期7卷 24-29页

作者： Zhihui XIE Nengyin SHENG naihe jing State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChineseAcademy of SciencesShanghai 200031China

The development of spinal cord is a precisely and sequentially regulated process, which is controlled bysignaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of BMP signaling in different stages of this developmental process. It is also clear that the proper functions of BMP signaling require its cross-talk with several other signaling pathways including Notch, Wnt and retinoic acid （RA） pathways. Here, we highlight the recent advancement in understanding the roles of BMP signaling during neurogenesis, neural tube patterning, axon development and glial differentiation in the spinal cord, and emphasize its integrations with other pathways during these processes.

关键词： BMP spinal cord neurogenesis patterning glia

Integration of Computational Analysis and Spatial Transcriptomics in Single-cell Studies

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 13-23页

作者： Ran Wang Guangdun Peng Patrick P.L.Tam naihe jing State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Embryology Research Unit Children’s Medical Research InstituteUniversity of SydneySydneyNSW 2145Australia School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSW 2145Australia Guangzhou Laboratory Guangzhou 510005China

Recent advances of single-cell transcriptomics technologies and allied computational methodologies have revolutionized molecular cell ***,pioneering explorations in spatial transcriptomics have opened up avenues to address fundamental biological questions in health and ***,we review the technical attributes of single-cell RNA sequencing and spatial transcriptomics,and the core concepts of computational data *** further highlight the challenges in the application of data integration methodologies and the interpretation of the biological context of the findings.

关键词： scRNA-seq Computational methodology Spatial transcriptome Data integration Mathematical model

The therapeutic prospects and challenges of human neural stem cells for the treatment of Alzheimer’s Disease

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Cell Regeneration 2022年第1期11卷 293-302页

作者： Chunmei Yue Su Feng Yingying Chen naihe jing State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Department of Biological Sciences School of ScienceXi’an Jiaotong-Liverpool UniversitySuzhou 215000China Bioland Laboratory/Guangzhou Laboratory Guangzhou 510005China CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

Alzheimer’s disease(AD)is a multifactorial neurodegenerative disorder associated with *** to its insidious onset,protracted progression,and unclear pathogenesis,it is considered one of the most obscure and intractable brain disorders,and currently,there are no effective therapies for *** evidence indicates that the irreversible decline of cognitive abilities in patients coincides with the deterioration and degeneration of neurons and synapses in the AD *** neural stem cells(NSCs)hold the potential to functionally replace lost neurons,reinforce impaired synaptic networks,and repair the damaged AD *** have therefore received extensive attention as a possible source of donor cells for cellular replacement therapies for ***,we review the progress in NSC-based transplantation studies in animal models of AD and assess the therapeutic advantages and challenges of human NSCs as donor *** then formulate a promising transplantation approach for the treatment of human AD,which would help to explore the disease-modifying cellular therapeutic strategy for the treatment of human AD.

关键词： Brain disorders Alzheimer’s disease Stem cell-based replacement therapy Neural subtype-specific transplantation Brain region-specific transplantation Cognitive ability

Derivation of Haploid Neurons from Mouse Androgenetic Haploid Embryonic Stem Cells

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Neuroscience Bulletin 2017年第3期33卷 361-364页

作者： He Xu Chunmei Yue Ting Zhang Yuanyuan Li Ao Guo Jiaoyang Liao Gang Pei Jinsong Li naihe jing State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University

Dear Editor,Haploid embryonic stem cells（ha ESCs）hold great potential for genetic screening and the analysis of recessive *** studies have recently reported the generation of mammalian ha ESCs through gamete manipul... 详细信息

关键词： recessive haploid genomics screening embryonic manipulation pluripotent maintenance panel Mouse

TGFβ signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse ESCs

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Journal of Molecular Cell Biology 2018年第3期10卷 216-228页

作者： Xianfa Yang Ran Wang Xiongjun Wang Guoqing Cai Yun Qian Su Feng Fangzhi Tan Kun Chen Ke Tang Xingxu Huang naihe jing Yunbo Qiao State Key Laboratory of Cell Biology CAS Center for ExceUence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai 200031 China School of Life Science and Technology ShanghaiTech University Shanghai 201210 China Precise Genome Engineering Center School of Life Sciences Guangzhou University Guangzhou 510006 China

Clinical therapies of pluripotent stem cells （PSCs）-based transplantation have been hindered by frequent development of terato- mas or tumors in animal models and clinical patients. Therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. Here we differentiate Oct4-GFP mouse embryonic stem cells （mESCs） into neural progenitor cells （NPCs） and find that a minority of Oct4＋ cells are continuously sustained at Oct4＋ state. These cells can be enriched and proliferated in a standard ESC medium. Interestingly, the differentiation potential of these enriched cells is tightly restricted with much higher tumorigenic activity, which are thus defined as differentiation-resistant ESCs （DR-ESCs）. Transcriptomic and epigenomic analyses show that DR-ESCs are characterized by primordial germ cell-like gene sig- natures （Dazl, Rec8, Stro8, BUmp1, etc.） and specific epigenetic patterns distinct from mESCs. Moreover, the DR-ESCs possess germ cell potential to generate Sycp3＋ haploid cells and are able to reside in sperm-free spermaduct induced by busulfan. Finally, we find that TGFβ signaling is overactivated in DR-ESCs, and inhibition of TGFβ signaling eliminates the tumorigenicity of mESC-derived NPCs by inducing the full differentiation of DR-ESCs. These data demonstrate that these TGFβ-hyperactivated germ ceU-like DR-ESCs are the main contributor for the tumorigenicity of ESCs-derived target cell therapy and that inhibition of TGFβ signaling in ESC-derived NPC transplantation could drastically reduce the risk of tumor development. Keywords： embryonic stem cells, differentiation-resistant ESCs, tumorigenicity, germ cell, TGFβ signaling

关键词： embryonic stem cells differentiation-resistant ESCs tumorigenicity germ cell TGFβ signaling

Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells

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Cell Regeneration 2023年第1期12卷 317-337页

作者： He Jax Xu Yao Yao Fenyong Yao Jiehui Chen Meishi Li Xianfa Yang Sheng Li Fangru Lu Ping Hu Shuijin He Guangdun Peng naihe jing State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences BeijingChina School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Center for Cell Lineage and Development CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGIBH‑HKU Guangdong‑Hong Kong Stem Cell and Regenerative Medicine Research CentreGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangzhou Laboratory/Bioland Laboratory Guangzhou 510005China Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 20023China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Center for Cell Lineage and Atlas Bioland LaboratoryGuangzhou 510005China

Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis(ALS),spinal muscular atrophy(SMA)and spinal cord injury(SCI).These disorders are currently incurable,while human pluripotent stem cells(hPSCs)-derived spinal motor neurons are promising but suffered from inappropriate regional identity and functional immaturity for the study and treatment of posterior spinal cord related *** this study,we have established human spinal cord neural progenitor cells(hSCNPCs)via hPSCs differentiated neuromesodermal progenitors(NMPs)and demonstrated the hSCNPCs can be continuously expanded up to 40 *** can be rapidly differentiated into posterior spinal motor neurons with high *** functional maturity has been examined in ***,a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction(NMJ)formation in ***,these studies highlight the potential avenues for generating clinically relevant spinal motor neurons and modeling neuromuscular diseases through our defined hSCNPCs.

关键词： Motor neuron Motor neuron differentiation Neuromesodermal progenitors Neuromuscular junction