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Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural Stem Cells by HMGA2/let-7b

Authors
 Kyung-Rok Yu ; Ji-Hee Shin ; Kyung-Sun Kang ; Dong Wook Han ; Sue Shin ; Sung Jun Jung ; Dong-Wook Kim ; Min Ki Jee ; Tae-hoon Shin ; SeungHee Lee ; Yoojin Seo ; Hyung-Sik Kim ; Soon Won Choi ; Jin Young Lee ; Myung Guen Koog ; Jae-Jun Kim 
Citation
 Cell Reports, Vol.10(3) : 441~452, 2015 
Journal Title
 Cell Reports 
ISSN
 2211-1247 
Issue Date
2015
Abstract
A recent study has suggested that fibroblasts can be converted into mouse-induced neural stem cells (miNSCs) through the expression of defined factors. However, successful generation of human iNSCs (hiNSCs) has proven challenging to achieve. Here, using microRNA (miRNA) expression profile analyses, we showed that let-7 microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies from human adult fibroblasts and the proliferation and self-renewal of hiNSCs. HMGA2, a let-7-targeting gene, enables induction of hiNSCs that displayed morphological/molecular features and in vitro/in vivo differentiation potential similar to H9-derived NSCs. Interestingly, HMGA2 facilitated the efficient conversion of senescent somatic cells or blood CD34+ cells into hiNSCs through an interaction with SOX2, whereas other combinations or SOX2 alone showed a limited conversion ability. Taken together, these findings suggest that HMGA2/let-7 facilitates direct reprogramming toward hiNSCs in minimal conditions and maintains hiNSC self-renewal, providing a strategy for the clinical treatment of neurological diseases.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140515
DOI
10.1016/j.celrep.2014.12.038
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Physiology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S2211124714010675
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