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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

The genome-wide molecular regulation of mouse gastrulation embryo

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Science China(Life Sciences) 2017年第4期60卷 363-369页

作者： Guangdun Peng naihe jing State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences

The diverse morphologies among vertebrate species stems from the evolution of a basic body plan that is constituted by a spatially organized ensemble of tissue lineage progenitors. At gastrulation, this body plan is established through a coordinated morphogenetic process and the delineation of tissue lineages that are driven by the activity of the genome. To explore the molecular mechanisms, in a comprehensive context, it is imperative to glean an understanding of the region-and population-specific genetic activity underpinning this fundamental developmental process. In this review, we outline the recent progress and the future directions in studies of genome activity for the regulation of mouse embryogenesis at gastrulation.

关键词：老鼠胚胎 gastrulation 干细胞系 transcriptome 风景早开发

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

Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling

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分子细胞生物学报:英文版 2015年第5期7卷 455-465页

作者： Lingyu Li Lu Song Chang Liu Jun Chen Guangdun Peng Ran Wang Pingyu Liu Ke Tang Janet Rossant naihe jing State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Institute of Life Science Nanchang UniversityNanchang 330031JiangxiChina Program in Developmental and Stem Cell Biology Hospital for Sick Children Research InstituteTorontoON M5G 1X8Canada Department of Developmental Biology Stanford University School of MedicineStanfordCA 94305USA

The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic *** recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its ***,we demonstrate that through brief inhibition of Nodal signaling in vitro,mouse embryonic stem cell(ESC)-derived epiblast stem cells(ESD-EpiSCs)could be committed to transient ectodermal progenitor populations,which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4,*** studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like ***,FGF–Erk signaling may also be alleviated during the generation of ectoderm-like ***,our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs,which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.

关键词： EpiSCs ectoderm BMP4 Nodal FGF

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

pluripotent 干细胞(PSC ) 的临床的治疗基于移植被 teratomas 或肿瘤的经常的开发在动物模型和临床的病人妨碍了。因此，在干细胞治疗澄清 carcinogenesis 的机制为减少 tumorigenicity 的风险是很重要的。这里，我们区分 Oct4-GFP 老... 详细信息

pluripotent 干细胞(PSC ) 的临床的治疗基于移植被 teratomas 或肿瘤的经常的开发在动物模型和临床的病人妨碍了。因此，在干细胞治疗澄清 carcinogenesis 的机制为减少 tumorigenicity 的风险是很重要的。这里，我们区分 Oct4-GFP 老鼠胚胎的干细胞(mESCs ) 进神经祖先房间(NPC ) 并且发现少数 Oct4+ 房间连续地以 Oct4+ 状态被支撑。这些房间能在标准转换字符媒介被充实并且增殖。有趣地，这些充实的房间的区别潜力紧与许多更高的 tumorigenic 活动被限制，它是因此定义的同样区别抵抗的转换字符(医生转换字符) 。Transcriptomic 和 epigenomic 分析证明医生转换字符被初发的细菌描绘像房间的基因签名(Dazl， Rec8， Stra8， Blimp1，等等) 并且从 mESCs 不同的特定的 epigenetic 模式。而且，医生转换字符拥有细菌房间潜力产生 Sycp3+ haploid 房间并且能居住在 busulfan 导致的没有精子的输精管。最后，我们发现 TGF 发信号是在 TGF 发信号的医生转换字符，和抑制的 overactivated 由导致医生转换字符的完整的区别消除导出 mESC 的 NPC 的 tumorigenicity。这些数据表明那像房间的医生转换字符是的这些 TGF-hyperactivated 细菌为导出转换字符的目标房间治疗的 tumorigenicity 和在导出转换字符的 NPC 移植发信号的 TGF 的那抑制的主要贡献者能急速地减少肿瘤开发的风险。

关键词： TGF 字符祖先神经老鼠干细胞治疗动物模型标准转换