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Using transcription factors for direct reprogramming of neurons in vitro 预览
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作者 Layal El Wazan Daniel Urrutia-Cabrera Raymond Ching-Bong Wong 《世界干细胞杂志:英文版(电子版)》 2019年第7期431-444,共14页
Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availab... Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availability.Direct reprogramming provides an exciting avenue to generate specialized neuron subtypes in vitro,which have the potential to be used for autologous transplantation,as well as generation of patient-specific disease models in the lab for drug discovery and testing gene therapy.Here we present a detailed review on transcription factors that promote direct reprogramming of specific neuronal subtypes with particular focus on glutamatergic,GABAergic,dopaminergic,sensory and retinal neurons.We will discuss the developmental role of master transcriptional regulators and specification factors for neuronal subtypes,and summarize their use in promoting direct reprogramming into different neuronal subtypes.Furthermore,we will discuss up-and-coming technologies that advance the cell reprogramming field,including the use of computational prediction of reprogramming factors,opportunity of cellular reprogramming using small chemicals and microRNA,as well as the exciting potential for applying direct reprogramming in vivo as a novel approach to promote neuro-regeneration within the body.Finally,we will highlight the clinical potential of direct reprogramming and discuss the hurdles that need to be overcome for clinical translation. 展开更多
关键词 Cell REPROGRAMMING Neuronal subtypes Transcription factors DIRECT REPROGRAMMING GLUTAMATERGIC NEURONS GABAERGIC NEURONS Retinal NEURONS
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Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review
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作者 Qijing LEI Qin PAN +4 位作者 Shuai YU Na LI Shulin CHEN Kuldip SIDHU Jinlian HUA 《农业科学与工程前沿:英文版》 2019年第1期28-32,共5页
Primordial germ cells(PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by ?rst dedifferentiation to embryonic germ ... Primordial germ cells(PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by ?rst dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells(iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established.Here, we discuss recent advances in the stem cell ?eld for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species. 展开更多
关键词 PIG PLURIPOTENT stem CELLS primordial GERM CELLS REPROGRAMMING
Sialylation is involved in cell fate decision during development, reprogramming and cancer progression
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作者 Fenjie Li Junjun Ding 《蛋白质与细胞:英文版》 SCIE CAS CSCD 2019年第8期550-565,共16页
Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenes... Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progressionSialylation is essential for early embryonic development and the deletion of UDP-GIcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision. 展开更多
关键词 SIALYLATION cell FATE DEVELOPMENT REPROGRAMMING cancer
Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor
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作者 Wei Tang Ren Guo +6 位作者 Shi-jun Shen Yang Zheng Yu-ting Lu Meng-meng Jiang Xue Cui Ci-zhong Jiang Xin Xie 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第5期620-629,共10页
Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we hav... Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we have generated hepatocyte-like cells from mouse fibroblasts using only one transcription factor (TF) plus a chemical cocktail. Here, we show that human urine-derived epithelial-like cells (hUCs) can also be transdifferentiated into human hepatocyte-like cells (hiHeps) using one TF (Foxa3, Hnf1α, or Hnf4α) plus the same chemical cocktail CRVPTD (C, CHIR99021;R, RepSox;V, VPA;P, Parnate;T, TTNPB;and D, Dznep). These hiHeps express multiple hepatocyte-specific genes and display functions characteristic of mature hepatocytes. With the introduction of the large T antigen, these hiHeps can be expanded in vitro and can restore liver function in mice with concanavalin-A-induced acute liver failure. Our study provides a strategy to generate functional hepatocyte-like cells from hUCs by using a single TF plus a chemical cocktail. 展开更多
关键词 REPROGRAMMING HEPATIC TRANSDIFFERENTIATION human urine-derived cells CHEMICAL cocktail regenerative medicine
哺乳动物早期胚胎发育中表观遗传信息的传递和重编程
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作者 卢绪坤 李元元 颉伟 《中国细胞生物学学报》 CAS CSCD 2019年第5期822-833,共12页
高度特化的精子和卵子如何重编程形成全能性的受精卵?受精卵又是如何通过时空有序的分裂和分化形成各种细胞谱系,进而发育成一个完整的个体?这些问题是生殖生物学、发育生物学乃至整个生命科学领域基本和关键的科学问题。近年来,随着技... 高度特化的精子和卵子如何重编程形成全能性的受精卵?受精卵又是如何通过时空有序的分裂和分化形成各种细胞谱系,进而发育成一个完整的个体?这些问题是生殖生物学、发育生物学乃至整个生命科学领域基本和关键的科学问题。近年来,随着技术的进步和研究的深入,人们可以从全基因组水平以前所未有的广度、深度和精度窥探这一过程中重要的分子事件。研究发现, DNA的微环境染色质及其所携带的表观遗传信息在这些过程中发生了剧烈的重编程,以完成亲代到子代的转换。DNA甲基化、组蛋白修饰、染色质开放程度以及染色质高级结构等表观遗传信息在配子发生和早期胚胎发育过程中经历了广泛的建立、擦除以及重建过程。同时,部分表观遗传信息可以从亲代传递到子代。该文总结了近年来在哺乳动物早期胚胎发育中表观遗传信息的传递和重编程方面取得的研究进展,同时阐述了表观遗传信息传递和重编程的潜在机制和生物学意义。 展开更多
关键词 DNA甲基化 组蛋白修饰 染色质开放程度 染色质高级结构 重编程 配子发生 早期胚胎发育
Esrrb plays important roles in maintaining self-renewal of trophoblast stem cells (TSCs) and reprogramming somatic cells to induced TSCs
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作者 Haibo Gao Rui Gao +7 位作者 Linfeng Zhang Wenchao Xiu Ruge Zang Hong Wang Yong Zhang Jiayu Chen Yawei Gao Shaorong Gao 《分子细胞生物学报:英文版》 SCIE CAS CSCD 2019年第6期463-473,共11页
Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essenti... Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essential insights into the molecular mechanisms controlling the placental development can be gained by using TSCs as the cell model. Esrrb is a transcription factor that has been shown to play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise mechanism whereby Esrrb regulates TSC-specific transcriptome during differentiation and reprogramming is still largely unknown. In the present study, we elucidate the function of Esrrb in self-renewal and differentiation of TSCs, as well as during the induced TSC (iTSC) reprogramming. We demonstrate that the precise level of Esrrb is critical for stem state maintenance and further trophoblast differentiation of TSCs, as ectopically expressed Esrrb can partially block the rapid differentiation of TSCs in the absence of fibroblast growth factor 4. However, Esrrb depletion results in downregulation of certain key TSC-specific transcription factors, consequently causing a rapid differentiation of TSCs and these Esrrb-deficient TSCs lose the ability of hemorrhagic lesion formation in vivo. This function of Esrrb is exerted by directly binding and activating a core set of TSC-specific target genes including Cdx2, Eomes, Sox2, Fgfr4, and Bmp4. Furthermore, we show that Esrrb overexpression can facilitate the MEF-to-iTSC conversion. Moreover, Esrrb can substitute for Eomes to generate GEsTM-iTSCs. Thus, our findings provide a better understanding of the molecular mechanism of Esrrb in maintaining TSC self-renewal and during iTSC reprogramming. 展开更多
关键词 Esrrb TROPHOBLAST stem cell self-renwwal DIFFERENTIATION iTSC REPROGRAMMING
Retrotransposon-mediated DELLA transcriptional reprograming underlies semi-dominant dwarfism in foxtail millet 预览
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作者 Meicheng Zhao Hui Zhi +2 位作者 Xue Zhang Guanqing Jia Xianmin Diao 《作物学报:英文版》 CAS CSCD 2019年第4期458-468,共11页
Retrotransposons account for a large proportion of the genome and genomic variation, and play key roles in creating novel genes and diversifying the genome in many eukaryotic species. Although retrotransposons are abu... Retrotransposons account for a large proportion of the genome and genomic variation, and play key roles in creating novel genes and diversifying the genome in many eukaryotic species. Although retrotransposons are abundant in plants, their roles had been underestimated because of a lack of research. Here, we characterized a gibberellin Acid (GA)-insensitive dwarf mutant, 84133, in foxtail millet. Map-based cloning revealed a 5.5-kb Copia-like retrotransposon insertion in DWARF1 (D1), which encodes a DELLA protein. Transcriptional analysis showed that the Copia retrotransposon mediated the transcriptional reprogramming of D1 leading to a novel N-terminal-deleted truncated DELLA transcript that was putatively driven by Copia's LTR, namely D1-TT, and another chimeric transcript. The presence of D1-TT was confirmed by protein immunodetection analysis. Furthermore, D1-TT protein was resistant to GA3 treatment compared with the intact DELLA protein due to its inability to interact with the GA receptor, SiGID1. Overexpression of D1-TT in foxtail millet resulted in dwarf plants, confirming that it determines the dwarfism of 84133. Thus, our study documents a rare instance of long terminal repeat (LTR) retrotransposon-mediated transcriptional reprograming in the plant kingdom. These results shed light on the function of LTR retrotransposons in generating new gene functions and genetic diversity. 展开更多
关键词 RETROTRANSPOSON TRANSCRIPTIONAL reprogramming DELLA Dwarf breeding Foxtail millet (Setaria italica)
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Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach
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作者 Chang Liu Xu Hu +7 位作者 Yawen Li Wenjie Lu Wenlin Li Nan Cao Saiyong Zhu Jinke Cheng Sheng Ding Mingliang Zhang 《分子细胞生物学报:英文版》 SCIE CAS CSCD 2019年第6期489-495,共7页
Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously est... Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy. 展开更多
关键词 small molecules reprogramming OLIGODENDROCYTE progenitor-like CELLS cell fate CONVERSION DEMYELINATING diseases
Human adult pluripotency:Facts and questions 预览
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作者 Luminita Labusca Kaveh Mashayekhi 《世界干细胞杂志:英文版(电子版)》 2019年第1期1-12,共12页
Cellular reprogramming and induced pluripotent stem cell(IPSC)technology demonstrated the plasticity of adult cell fate,opening a new era of cellular modelling and introducing a versatile therapeutic tool for regenera... Cellular reprogramming and induced pluripotent stem cell(IPSC)technology demonstrated the plasticity of adult cell fate,opening a new era of cellular modelling and introducing a versatile therapeutic tool for regenerative medicine.While IPSCs are already involved in clinical trials for various regenerative purposes,critical questions concerning their medium-and long-term genetic and epigenetic stability still need to be answered.Pluripotent stem cells have been described in the last decades in various mammalian and human tissues(such as bone marrow,blood and adipose tissue).We briefly describe the characteristics of human-derived adult stem cells displaying in vitro and/or in vivo pluripotency while highlighting that the common denominators of their isolation or occurrence within tissue are represented by extreme cellular stress.Spontaneous cellular reprogramming as a survival mechanism favoured by senescence and cellular scarcity could represent an adaptative mechanism.Reprogrammed cells could initiate tissue regeneration or tumour formation dependent on the microenvironment characteristics.Systems biology approaches and lineage tracing within living tissues can be used to clarify the origin of adult pluripotent stem cells and their significance for regeneration and disease. 展开更多
关键词 HUMAN ADULT PLURIPOTENT STEM CELLS Induced PLURIPOTENT STEM CELLS Reprogramming Cellular stress
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Intrinsic fluctuation and susceptibility in somatic cell reprogramming process
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作者 沈健 张小敏 +3 位作者 李齐亮 王歆宇 赵蕴杰 贾亚 《中国物理B:英文版》 SCIE EI CAS CSCD 2019年第4期113-120,共8页
Based on the coherent feedforward transcription regulation loops in somatic cell reprogramming process, a stochastic kinetic model is proposed to study the intrinsic fluctuations in the somatic cell reprogramming. The... Based on the coherent feedforward transcription regulation loops in somatic cell reprogramming process, a stochastic kinetic model is proposed to study the intrinsic fluctuations in the somatic cell reprogramming. The Fano factor formulas of key genes expression level in the coherent feedforward transcription regulation loops are derived by using of Langevin theory. It is found that the internal fluctuations of gene expression levels mainly depend on itself activation ratio and degradation ratio. When the self-activation ratio(or self-degradation ratio) is increased, the Fano factor increases reaches a maximum and then decreases. The susceptibility is used to measure the sensitivity of steady-state response to the variation in systemic parameters. It is found that with the increase of the self-activation ratio(or self-degradation ratio), the susceptibility of steady-state increases at first, it reaches a maximum, and it then decreases. The magnitude of the maximum is increased with the increase of activated ratio by the upstream transcription factor. 展开更多
关键词 INTRINSIC FLUCTUATION SUSCEPTIBILITY coherent FEEDFORWARD LOOPS somatic cell REPROGRAMMING
Differential neuronal reprogramming induced by NeuroD1 from astrocytes in grey matter versus white matter 预览
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作者 Min-Hui Liu Wen Li +3 位作者 Jia-Jun Zheng Yu-Ge Xu Qing He Gong Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期342-351,共10页
A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial ... A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018. 展开更多
关键词 ASTROCYTE CONVERSION efficiency corpus callosum cortex grey MATTER in vivo cell CONVERSION NeuroD1 neuron REPROGRAMMING STRIATUM white MATTER
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核移植技术的建立与发展
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作者 廖兆蒂 刘真 孙强 《中国细胞生物学学报》 CAS CSCD 2019年第6期1032-1040,共9页
核移植技术是指通过显微操作技术将供体细胞核转移到去核卵母细胞,进而获得重构胚胎的过程。从上世纪50年代开始到现在,核移植技术得到了广泛的发展和深入的研究,并在生命科学的多个领域发挥重要的作用。核移植技术的建立与发展可分为... 核移植技术是指通过显微操作技术将供体细胞核转移到去核卵母细胞,进而获得重构胚胎的过程。从上世纪50年代开始到现在,核移植技术得到了广泛的发展和深入的研究,并在生命科学的多个领域发挥重要的作用。核移植技术的建立与发展可分为两个阶段:起始阶段开始于卵体积较大的两栖动物。这一阶段核移植技术主要用来研究细胞核的功能及与胞质之间相互作用。其后核移植技术在哺乳动物中的应用促进了该技术的更深入发展。相对于两栖动物,核移植技术在哺乳动物中的研究和应用也呈现更加深入、多元的特点。主要包括:不同哺乳动物物种及不同供体细胞类型的克隆研究;显微操作技术的发展和完善;重编程机制的研究及核移植效率的提高;核移植在濒危物种保护、个性化干细胞治疗及遗传修饰动物模型构建方面的应用等。该文将就这两个阶段核移植技术的发展历程进行综述并对其在非人灵长类动物模型构建中的应用进行展望。 展开更多
关键词 核移植 显微操作技术 两栖动物 哺乳动物 重编程 非人灵长类动物
Anti-aging theory of quantum nature and brain reprogramming 预览
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作者 Yurii Pozniak 《TMR生命研究》 2019年第3期113-118,共6页
As many scientists believe, human aging is a very important part of the program of life-human activity rather than a disease. The human brain may be the controller, performer and participant of the natural program of ... As many scientists believe, human aging is a very important part of the program of life-human activity rather than a disease. The human brain may be the controller, performer and participant of the natural program of life-human activity, from birth to death. The program of life-activities of the brain and the human body is very similar to a conventional computer program and it may also be malfunctioning. The work of the natural program of life-activity resembles the work of AI. Each program of life-activity of an individual is repeatedly subjected to natural correction of program tasks in the life of a biophysical being. However, in recent years, scientists from different countries began to seek to reprogram the brain and find the real cause of death. Some biologists and evolutionists believe that this process is nonrandom and that it is controlled by a kind of “death program.” So they call a special set of genes, forcing the body to become decrepit and die, giving way to a new generation of their own kind. The aim of our work is to design new technologies and methods to adjust the life-activity programs from biophysical views, increasing the useful life of bodies by delaying destructive processes and the aging process. Our life-activity program is carried out through the device and IT programs in a mobile application, using contact/contactless frequency code eff ects on the brain, which is decoded and accepted by the human brain for execution (reprogramming), as a natural addition and an integral part of the brain work. Code programs are compiled according to the working algorithms of the Cosmo-terrestrial structure of life-activity of biophysical objects on the planet Earth. Our technology is one of the varieties of brain-computer technology. 展开更多
关键词 BRAIN REPROGRAMMING QUANTUM medical BIOPHYSICS Armarium
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Efficient derivation of extended pluripotent stem cells from NOD-scid II2rg-/-mice
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作者 Yaqin Du Ting Wang +10 位作者 Jun Xu Chaoran Zhao Haibo Li Yao Fu Yaxing Xu Liangfu Xie Jingru Zhao Weifeng Yang Ming Yin Jinhua Wen Hongkui Deng 《蛋白质与细胞:英文版》 SCIE CAS CSCD 2019年第1期31-42,共12页
Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and ge... Recently we have established a new culture condition enabling the derivation of extended pluripotent stem(EPS)cells,which,compared to conventional pluripotent stem cells,possess superior developmental potential and germline competence.However,it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment.Here,we show that EPS cells can be robustly generated from non-permissive NOD-sc/d Il2rg 1 mice through de novo derivation from blastocysts.Furthermore,these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-sc/d II2rg-/-fibroblasts.NOD-sc/d II2rg-/-EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting.Notably,these cells contribute to both embryonic and extraembryonic lineages in vivo.More importantly,they can produce chimeras and integrate into the E13.5 genital ridge.Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains,which could potentially be a general strategy for deriving mouse pluripotent cells.The generation of NOD-sc/d II2rg-/-Yaqin Du and Ting Wang contributed equally to this work.Electronic supplementary material The online version of this article(https://doi.org/10.1007/s13238-018-0558-z)contains supplementary material,which is available to authorized users.EPS cell lines permits sophisticated genetic modification in NOD-scid II2rg-/-mice,which may greatly advance the optimization of humanized mouse models for biomedical applications. 展开更多
关键词 EXTENDED PLURIPOTENT stem cell NOD-scid II2rg-/-mice EMBRYONIC and extraembryonic LINEAGES chemical REPROGRAMMING
原发性硬化性胆管炎疾病源性iPSCs细胞模型的建立 预览
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作者 孙艳 石光 +3 位作者 胡春梅 张雪 顾佳颖 迟宝荣 《胃肠病学和肝病学杂志》 CAS 2019年第5期552-555,共4页
目的探讨原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)疾病源性诱导性多能干细胞(induced pluripotent stem cells,iPSCs)细胞模型的建立。方法采用Oct3/4、Sox2、c-Myc和Klf44种转录因子,以仙台病毒为载体重编程PSC患者皮... 目的探讨原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)疾病源性诱导性多能干细胞(induced pluripotent stem cells,iPSCs)细胞模型的建立。方法采用Oct3/4、Sox2、c-Myc和Klf44种转录因子,以仙台病毒为载体重编程PSC患者皮肤成纤维细胞,获得疾病特异性的iPSCs细胞,并对其生物学特性进行鉴定。结果PSC疾病源性的iPSCs细胞呈典型胚胎干细胞样克隆,流式细胞分析显示高表达Oct4、TRA-1-81、SSEA和Nanog等胚胎干细胞标志性抗原,体外向内、中、外三个胚层诱导分化后均检测到各胚层标志抗原的表达,传代过程中保持稳定正常的染色体核型。结论应用Yamanaka因子和仙台病毒载体成功建立PSC疾病源性iPSCs细胞模型,后续进一步向胆管细胞诱导分化可用于研究疾病的发病机制。 展开更多
关键词 原发性硬化性胆管炎 重编程 诱导性多能干细胞
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优化建立猪多能性细胞及向神经谱系细胞特异性分化
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作者 李雪 张犇 +6 位作者 牛淑冬 王玉阁 文丽波 梁晨 齐晓娟 李宇 雷蕾 《解剖学报》 CAS CSCD 北大核心 2019年第1期24-28,共5页
目的探讨建立猪多能性细胞(iPPCs)的优化方案,并探求其向神经谱系细胞特异性分化的方法。方法利用经典的Yamanaka方法,联合应用组蛋白乙酰化酶抑制剂丙戊酸(VPA)、甲基转移酶抑制剂5-氮-2’-脱氧胞苷(5-AZA)及Oct4病毒的重复感染,优化... 目的探讨建立猪多能性细胞(iPPCs)的优化方案,并探求其向神经谱系细胞特异性分化的方法。方法利用经典的Yamanaka方法,联合应用组蛋白乙酰化酶抑制剂丙戊酸(VPA)、甲基转移酶抑制剂5-氮-2’-脱氧胞苷(5-AZA)及Oct4病毒的重复感染,优化重编程方案,诱导巴马小型猪胚胎成纤维细胞为诱导的iPPCs。通过Real-time PCR检测重编程过程中多能性基因的分子表达。通过维甲酸(RA)及细胞外基质(ECM)的联合培养,诱导iPPCs向神经谱系细胞特异性分化,免疫荧光细胞化学方法检测神经特异性标记物表达。结果应用优化方案,将猪胚胎成纤维细胞重编程为iPPCs。Real-time PCR显示,VPA和Oct4病毒的重复感染可显著促进重编程过程中多潜能基因的表达。5-AZA未显著提高多潜能基因的表达。RA及ECM的联合培养可诱导iPPCs向神经谱系细胞分化,并表达神经特异性标志基因神经元类型Ⅲβ-微管蛋白(Tuj1)和胶质纤维酸性蛋白(GFAP)。结论在利用优化方案建立猪多能性细胞的基础上,将其向神经谱系细胞特异性分化,对人类神经性疾病的细胞替代治疗具有重要意义。 展开更多
关键词 胚胎成纤维细胞 重编程 诱导多能性细胞 神经分化 维甲酸 免疫荧光
Induced pluripotent stem cells throughout the animal kingdom: Availability and applications 预览
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作者 Lais Vicari de Figueiredo Pessoa Fabiana Fernandes Bressan Kristine Karla Freude 《世界干细胞杂志:英文版(电子版)》 2019年第8期491-505,共15页
Up until the mid 2000s, the capacity to generate every cell of an organism was exclusive to embryonic stem cells. In 2006, researchers Takahashi and Yamanaka developed an alternative method of generating embryonic-lik... Up until the mid 2000s, the capacity to generate every cell of an organism was exclusive to embryonic stem cells. In 2006, researchers Takahashi and Yamanaka developed an alternative method of generating embryonic-like stem cells from adult cells, which they coined induced pluripotent stem cells (iPSCs). Such iPSCs possess most of the advantages of embryonic stem cells without the ethical stigma associated with derivation of the latter. The possibility of generating “custom-made” pluripotent cells, ideal for patient-specific disease models, alongside their possible applications in regenerative medicine and reproduction, has drawn a lot of attention to the field with numbers of iPSC studies published growing exponentially. IPSCs have now been generated for a wide variety of species, including but not limited to, mouse, human, primate, wild felines, bovines, equines, birds and rodents, some of which still lack well-established embryonic stem cell lines. The paucity of robust characterization of some of these iPSC lines as well as the residual expression of transgenes involved in the reprogramming process still hampers the use of such cells in species preservation or medical research, underscoring the requirement for further investigations. Here, we provide an extensive overview of iPSC generated from a broad range of animal species including their potential applications and limitations. 展开更多
关键词 PLURIPOTENCY EMBRYONIC Stem cell REPROGRAMMING ANIMAL Wild Induced PLURIPOTENCY
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父源基因组重编程中组蛋白变体的作用
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作者 王楠 黄星卫 +3 位作者 程香荣 姜琦 庞楠 雷蕾 《解剖学报》 CAS CSCD 北大核心 2019年第1期132-136,共5页
卵母细胞具有重编程精子基因组以确保胚胎正常发育的能力。精子入卵后,父源基因组会经历组蛋白替换鱼精蛋白,全基因组去甲基化等过程,从而启动胚胎发育。组蛋白H3的变体H3.3可以替换核小体中的典型组蛋白H3.1和H3.2,从而修饰染色质结构... 卵母细胞具有重编程精子基因组以确保胚胎正常发育的能力。精子入卵后,父源基因组会经历组蛋白替换鱼精蛋白,全基因组去甲基化等过程,从而启动胚胎发育。组蛋白H3的变体H3.3可以替换核小体中的典型组蛋白H3.1和H3.2,从而修饰染色质结构和影响基因表达。在早期胚胎发育过程中H3.3的缺失将导致染色体的过度凝集和错误分离。我们综述了组蛋白变体H3.3及其分子伴侣在精子发生、受精和早期胚胎发育中的作用,特别是H3.3对父源基因组重编程的重要性,这对理解受精后全能性合子的形成及着床前发育具有重要意义。 展开更多
关键词 受精 组蛋白 重编程 鱼精蛋白
Induced pluripotent stem cells,a giant leap for mankind therapeutic applications 预览
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作者 JoséBraganca Joao AndréLopes +1 位作者 Leonardo Mendes-Silva Joao Miguel Almeida Santos 《世界干细胞杂志:英文版(电子版)》 2019年第7期421-430,共10页
Induced pluripotent stem cells(iPSC)technology has propelled the field of stem cells biology,providing new cells to explore the molecular mechanisms of pluripotency,cancer biology and aging.A major advantage of human ... Induced pluripotent stem cells(iPSC)technology has propelled the field of stem cells biology,providing new cells to explore the molecular mechanisms of pluripotency,cancer biology and aging.A major advantage of human iPSC,compared to the pluripotent embryonic stem cells,is that they can be generated from virtually any embryonic or adult somatic cell type without destruction of human blastocysts.In addition,iPSC can be generated from somatic cells harvested from normal individuals or patients,and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible before.Besides these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells,these cells hold an immense potential for cell-based therapies,and for the discovery of new or personalized pharmacological treatments for many disorders.Here,we review some of the current challenges and concerns about iPSC technology.We introduce the potential held by iPSC for research and development of novel health-related applications.We briefly present the efforts made by the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation,characterization and long-term preservation.Finally,we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells. 展开更多
关键词 Induced PLURIPOTENT STEM cells REPROGRAMMING Cell-based therapy STEM cell BANKING Disease MODELLING
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Plasmid-based generation of neural cells from human fibroblasts using non-integrating episomal vectors 预览
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作者 Shao-Bing Dai Ting Shen +2 位作者 Ting-Ting Zheng Jia-Li Pu Xin-Zhong Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第3期501-505,共5页
Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, alth... Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine. 展开更多
关键词 nerve REGENERATION induced neurons plasmid-based human FIBROBLASTS NUCLEOFECTION Ascl1 miR124 p53 REPROGRAMMING neural REGENERATION
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