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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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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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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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Effect of Biophysical Cues on Cell Reprogramming
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作者 Yang Song Song Li 《医用生物力学》 CAS CSCD 北大核心 2019年第A01期14-15,共2页
Cell reprograming technologies have broad applications in cell therapy,disease modeling and drug screening.Direct reprogramming is the process of converting from one cell type into a very distantly related cell type.I... Cell reprograming technologies have broad applications in cell therapy,disease modeling and drug screening.Direct reprogramming is the process of converting from one cell type into a very distantly related cell type.In this direct conversion process,cells do not proceed through a pluripotent stage,which can be time-consuming and challenging due to spontaneous differentiation.This method also offers the advantage of circumventing the teratoma potential that is associated with using iPSCs.Previous works have demonstrated that with the use of genetic manipulation,fibroblasts can be directly converted into other cell types,including neurons,cardiomyocytes,blood cell progenitors,and hepatocytes.It is well known that the microenvironment can directs cell fate,and in turn cells interact with or remodel their niches.Accumulative evidence suggests that biophysical factors such as the microtopography and mechanical property of cell adhesive substrates regulate a variety of cellular functions such as migration,proliferation and differentiation,which in turn can modulate wound healing,tissue remodeling and tumor growth,but there are limited number of studies on the roles of biophysical cues in cell reprogramming[1].Passive topographical cues offer a simple and effective method to improve reprogramming efficiency without the need for biochemical manipulations.Our previous study has demonstrated that somatic cells cultured on the parallel microgrooves,which can replace the effects of small-molecule epigenetic modifiers and significantly improve the iPSCs reprogramming efficiency.The mechanism relies on the mechanomodulation of the cells’epigenetic state,specifically,an increase of histone H3 acetylation and H3K4 methylation[2].Additionally,in cardiomyocytes reprogramming study,culturing the fibroblasts on microgrooved substrate enhances the expression of cardiomyocyte genes by day 2 and improves the yield of partially reprogrammed cells at day 10.By combining microgrooved substrate with an optimized culture protocol,the conv 展开更多
关键词 EFFECT BIOPHYSICAL CUES CELL REPROGRAMMING
Using induced pluripotent stem cells for modeling Parkinson’s disease 预览
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作者 Minjing Ke Cheong-Meng Chong Huanxing Su 《世界干细胞杂志:英文版(电子版)》 2019年第9期634-649,共16页
Parkinson’s disease(PD)is an age-related neurodegenerative disease caused by the progressive loss of dopaminergic(DA)neurons in the substantia nigra.As DA neurons degenerate,PD patients gradually lose their ability o... Parkinson’s disease(PD)is an age-related neurodegenerative disease caused by the progressive loss of dopaminergic(DA)neurons in the substantia nigra.As DA neurons degenerate,PD patients gradually lose their ability of movement.To date no effective therapies are available for the treatment of PD and its pathogenesis remains unknown.Experimental models that appropriately mimic the development of PD are certainly needed for gaining mechanistic insights into PD pathogenesis and identifying new therapeutic targets.Human induced pluripotent stem cells(iPSCs)could provide a promising model for fundamental research and drug screening.In this review,we summarize various iPSCs-based PD models either derived from PD patients through reprogramming technology or established by gene-editing technology,and the promising application of iPSC-based PD models for mechanistic studies and drug testing. 展开更多
关键词 Parkinson’s disease DOPAMINERGIC neurons Induced PLURIPOTENT stem cells SOMATIC cell REPROGRAMMING Aging
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Impelling force and current challenges by chemicals in somatic cell reprogramming and expansion beyond hepatocytes 预览
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作者 Jian-Yun Ge Yun-Wen Zheng +2 位作者 Li-Ping Liu Hiroko Isoda Tatsuya Oda 《世界干细胞杂志:英文版(电子版)》 2019年第9期650-665,共16页
In the field of regenerative medicine,generating numerous transplantable functional cells in the laboratory setting on a large scale is a major challenge.However,the in vitro maintenance and expansion of terminally di... In the field of regenerative medicine,generating numerous transplantable functional cells in the laboratory setting on a large scale is a major challenge.However,the in vitro maintenance and expansion of terminally differentiated cells are challenging because of the lack of specific environmental and intercellular signal stimulations,markedly hindering their therapeutic application.Remarkably,the generation of stem/progenitor cells or functional cells with effective proliferative potential is markedly in demand for disease modeling,cell-based transplantation,and drug discovery.Despite the potent genetic manipulation of transcription factors,integration-free chemically defined approaches for the conversion of somatic cell fate have garnered considerable attention in recent years.This review aims to summarize the progress thus far and discuss the advantages,limitations,and challenges of the impact of full chemicals on the stepwise reprogramming of pluripotency,direct lineage conversion,and direct lineage expansion on somatic cells.Owing to the current chemical-mediated induction,reprogrammed pluripotent stem cells with reproducibility difficulties,and direct lineage converted cells with marked functional deficiency,it is imperative to generate the desired cell types directly by chemically inducing their potent proliferation ability through a lineagecommitted progenitor state,while upholding the maturation and engraftment capacity posttransplantation in vivo.Together with the comprehensive understanding of the mechanism of chemical drives,as well as the elucidation of specificity and commonalities,the precise manipulation of the expansion for diverse functional cell types could broaden the available cell sources and enhance the cellular function for clinical application in future. 展开更多
关键词 Chemical INDUCTION PLURIPOTENT REPROGRAMMING DIRECT LINEAGE conversion DIRECT LINEAGE EXPANSION Hepatocyte EXPANSION Cell fate specificity Transcriptional memory In vivo INDUCTION
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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
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
淫羊藿苷对小鼠皮肤成纤维细胞重编程为心肌样细胞的作用
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作者 赵星阳 谈佳岩 +3 位作者 李翰耕 叶蓉蓉 秦存兰 刘慧雯 《解剖科学进展》 2019年第5期497-501,共5页
目的研究小鼠成纤维细胞重编程为心肌样细胞(induced cardiomyocytes,iCMs)过程中淫羊藿苷(icariin,ICA)的作用及心血管发育中胚层相关蛋白1(mesoderm posterior 1,Mesp1)的表达。方法 MTT法筛选ICA的最佳药物浓度。GMT转染小鼠皮肤成... 目的研究小鼠成纤维细胞重编程为心肌样细胞(induced cardiomyocytes,iCMs)过程中淫羊藿苷(icariin,ICA)的作用及心血管发育中胚层相关蛋白1(mesoderm posterior 1,Mesp1)的表达。方法 MTT法筛选ICA的最佳药物浓度。GMT转染小鼠皮肤成纤维细胞,建立重编程心肌样细胞模型。qRT-PCR检测转染后重编程细胞中肌球蛋白重链6(myosin heavy chain 6, Myh6)的mRNA表达,免疫荧光细胞化学方法检测心肌肌钙蛋白I (cardiac troponinI, cTnI)及Mesp1的表达情况。结果 ICA最佳药物浓度为10-7mol/L。ICA组诱导iCMs高表达cTnI,是GMT组的1.3倍。Myh6 mRNA在重编程第3周达到高峰,且ICA组显著高于GMT组(P<0.01)。Mesp1与c TnI的表达趋势正好相反。结论 ICA可以提高成纤维细胞重编程为心肌样细胞的效率;Mesp1参与促进成纤维细胞重编程的过程。 展开更多
关键词 成纤维细胞 心肌细胞 重编程 淫羊藿苷 Mesp1 小鼠
SV40T促进施旺细胞重编程为间充质干细胞 预览
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作者 生立平 李瑞芳 +3 位作者 鄢艳红 杨娟 胡晴 葛林通 《基础医学与临床》 CSCD 2019年第10期1417-1422,共6页
目的鉴于施旺细胞(SCs)在外周神经损伤修复中发挥关键作用,本研究旨在通过猿猴病毒40大T抗原(SV40T)建立永生化的小鼠坐骨神经施旺细胞系及探讨其分化潜能。方法通过MPH 86质粒转染小鼠坐骨神经SCs,然后使用潮霉素筛选细胞并传代培养,... 目的鉴于施旺细胞(SCs)在外周神经损伤修复中发挥关键作用,本研究旨在通过猿猴病毒40大T抗原(SV40T)建立永生化的小鼠坐骨神经施旺细胞系及探讨其分化潜能。方法通过MPH 86质粒转染小鼠坐骨神经SCs,然后使用潮霉素筛选细胞并传代培养,将转染SV40T的SCs指定为SV40T-SCs。利用WST-1检测细胞增殖,并通过qPCR分析细胞SV40T及神经标志物的表达情况。将SV40T-SCs进行免疫组织化学染色。最后,在体外诱导SV40T-SCs进一步分化。结果SV40T-SCs的细胞形态多样,增殖迅速,可以永续传代,与原代SCs显著不同。SV40T-SCs高表达Nestin、Pax3和Slug。免疫组织化学染色显示CD44、CD73和CD105阳性。另外,SV40T-SCs在体外可被诱导分化为骨细胞和脂肪细胞。结论SV40T可能诱导小鼠坐骨神经SCs发生重编程作用,使SCs转化成为间充质干细胞(MSCs)。 展开更多
关键词 施旺细胞 SV40T 永生化 重编程 间充质干细胞
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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
Genomic integrity of human induced pluripotent stem cells:Reprogramming,differentiation and applications 预览
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作者 Clara Steichen Zara Hannoun +2 位作者 Eléanor Luce Thierry Hauet Anne Dubart-Kupperschmitt 《世界干细胞杂志:英文版(电子版)》 2019年第10期729-747,共19页
Ten years after the initial generation of induced pluripotent stem cells(hiPSCs)from human tissues,their potential is no longer questioned,with over 15000 publications listed on PubMed,covering various fields of resea... Ten years after the initial generation of induced pluripotent stem cells(hiPSCs)from human tissues,their potential is no longer questioned,with over 15000 publications listed on PubMed,covering various fields of research;including disease modeling,cell therapy strategies,pharmacology/toxicology screening and 3D organoid systems.However,despite evidences that the presence of mutations in hiPSCs should be a concern,publications addressing genomic integrity of these cells represent less than 1%of the literature.After a first overview of the mutation types currently reported in hiPSCs,including karyotype abnormalities,copy number variations,single point mutation as well as uniparental disomy,this review will discuss the impact of reprogramming parameters such as starting cell type and reprogramming method on the maintenance of the cellular genomic integrity.Then,a specific focus will be placed on culture conditions and subsequent differentiation protocols and how their may also trigger genomic aberrations within the cell population of interest.Finally,in a last section,the impact of genomic alterations on the possible usages of hiPSCs and their derivatives will also be exemplified and discussed.We will also discuss which techniques or combination of techniques should be used to screen for genomic abnormalities with a particular focus on the necessary quality controls and the potential alternatives. 展开更多
关键词 Induced PLURIPOTENT stem cells GENOMIC integrity MUTATIONS KARYOTYPE DIFFERENTIATION Cell therapy Quality control REPROGRAMMING
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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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