Background Since an effective method for generating induced pluripotent stem cells （iPSCs） from human neural stem cells （hNSCs） can offer us a promising tool for studying brain diseases, here we reported direct re...Background Since an effective method for generating induced pluripotent stem cells （iPSCs） from human neural stem cells （hNSCs） can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors. Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors （OCT3/4, SOX2, KLF4, and c-MYC）, iPSCs colonies were successfully obtained. Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo. Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.展开更多
Embryonic and induced pluripotent stem cells （ESCs and iPSCs） hold great promise for regenerative medi- cine. The therapeutic application of these cells requires an understanding of the molecular networks that regu-...Embryonic and induced pluripotent stem cells （ESCs and iPSCs） hold great promise for regenerative medi- cine. The therapeutic application of these cells requires an understanding of the molecular networks that regu- late pluripotency, differentiation, and de-differentiation. Along with signaling pathways, transcription factors, and epigenetic regulators, microRNAs （miRNAs） are emerging as important regulators in the establishment and maintenance of pluripotency. These tiny RNAs control proliferation, survival, the cell cycle, and the pluripotency program of ESCs. In addition, they serve as barriers or factors to overcome barriers during the reprogramming process. Systematic screening for novel miRNAs that regulate the establishment and mainte- nance of pluripotent stem cells and further mechanistic investigations will not only shed new light on the biology of ESCs and iPSCs, but also help develop safe and efficient technologies to manipulate cell fate for regen- erative medicine.展开更多
基金This work was supported by grants from the Major State Basic Research Program （No. 2010CB945500, No. 2012CB966300, and No. 2009CB941100）, the National Natural Science Foundation of China （No. 81271003 and No. 81200936）, Shanghai Committee of Science and Technology （No. 08dj140053）, and 2011 Shanghai Medical College Young Scientist Fund of Fudan University （11L-24）.Acknowledgements： We are grateful to technicians CHEN Lu-ping, SHEN Yi-wen and TANG Qi-sheng in our lab for their kind assistance in animal preparation and cell culture. We also thank Dr. SHA Hong-ying for picture processing and helpful comments and suggestions.
文摘Background Since an effective method for generating induced pluripotent stem cells （iPSCs） from human neural stem cells （hNSCs） can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors. Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors （OCT3/4, SOX2, KLF4, and c-MYC）, iPSCs colonies were successfully obtained. Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo. Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.
文摘Embryonic and induced pluripotent stem cells （ESCs and iPSCs） hold great promise for regenerative medi- cine. The therapeutic application of these cells requires an understanding of the molecular networks that regu- late pluripotency, differentiation, and de-differentiation. Along with signaling pathways, transcription factors, and epigenetic regulators, microRNAs （miRNAs） are emerging as important regulators in the establishment and maintenance of pluripotency. These tiny RNAs control proliferation, survival, the cell cycle, and the pluripotency program of ESCs. In addition, they serve as barriers or factors to overcome barriers during the reprogramming process. Systematic screening for novel miRNAs that regulate the establishment and mainte- nance of pluripotent stem cells and further mechanistic investigations will not only shed new light on the biology of ESCs and iPSCs, but also help develop safe and efficient technologies to manipulate cell fate for regen- erative medicine.
