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外科片麻醉手术科云南省第一人民医院[4]National Engineering Research Center of Biomedicine and Animal Science, Kunming, Yunnan, 650500, China
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.
基金:
This work was funded
by grants from the Chinese Ministry of Science and Technology 973
program (2012CBA01300), the Key Technologies Research and
Development Program of China (2014BAI03B01), the National
Natural Science Foundation of China (31360231), Yunnan Basic
Research Projects (2014FC004) and Yunnan Innovation Talents of
Science and Technology (2014HB054).
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
共同第一作者:
通讯作者:
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.
推荐引用方式(GB/T 7714):
Ai Zongyong,Xiang Zheng,Li Yuemin,et al.Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells[J].BIOMATERIALS.2016,77:53-65.doi:10.1016/j.biomaterials.2015.10.079.
APA:
Ai, Zongyong,Xiang, Zheng,Li, Yuemin,Liu, Guoku,Wang, Hong...&Li, Tianqing.(2016).Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells.BIOMATERIALS,77,
MLA:
Ai, Zongyong,et al."Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells".BIOMATERIALS 77.(2016):53-65