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Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells

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机构: [1]Yunnan Key Lab of Primate Biomedicine Research,Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China [2]Chongqing Key Lab of Forage & Herbivore, College of Animal Science and Technology (CAST), Southwest University, No. 1 Tiansheng Road Beibei, Chongqing, 400715, China [3]Department of Anesthesiology, No. 157, Jinbi Road, The First People Hospital of Yunnan Province, Kunming, Yunnan, 650032, China [4]National Engineering Research Center of Biomedicine and Animal Science, Kunming, Yunnan, 650500, China
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关键词: Monkey fibroblasts Telencephalic neuroepithelial stem cells Transdifferentiation Neural tubes Neural regeneration in vivo Cortical neuron

摘要:
Non-human primates provide optimal models for the development of stem cell therapies. Although somatic cells have been converted into neural stem/progenitor cells, it is unclear whether telencephalic neuroepithelial stem cells (NESCs) with stable properties can be generated from fibroblasts in primate. Here we report that a combination of transcription factors (Oct4, Sox2, Klf4) with a new culture medium induces rhesus monkey fibroblasts into NESCs, which can develop into miniature neural tube (NT)-like structures at a cell level. Furthermore, single induced NESCs (iNESCs) can generate later-stage 3D-NTs after grown on matrigel in suspension culture. iNESCs express NT cell markers, have a unique gene expression pattern biasing towards telencephalic patterning, and give rise to cortical neurons. Via transplantation, single iNESCs can extensively survive, regenerate myelinated neuron axons and synapse structures in adult monkey striatum and cortex, and differentiate into cortical neurons. Successful transplantation is closely associated with graft regions and grafted cell identities. The ability to generate defined and transplantable iNESCs from primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and cell therapy. (C) 2015 Elsevier Ltd. All rights reserved.

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出版当年[2016]版:
大类 | 1 区 工程技术
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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出版当年[2015]版:
Q1 MATERIALS SCIENCE, BIOMATERIALS Q1 ENGINEERING, BIOMEDICAL
最新[2023]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Yunnan Key Lab of Primate Biomedicine Research,Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China [4]National Engineering Research Center of Biomedicine and Animal Science, Kunming, Yunnan, 650500, China
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通讯机构: [1]Yunnan Key Lab of Primate Biomedicine Research,Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China [4]National Engineering Research Center of Biomedicine and Animal Science, Kunming, Yunnan, 650500, China [*1]Yunnan Key Lab of Primate Biomedicine Research,Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
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