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

Title
Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural Stem Cells by HMGA2/let-7b
Author
정승준
Issue Date
2015-01
Publisher
CELL PRESS
Citation
CELL REPORTS, v. 10, NO 3, Page. 441-452
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://hdl.handle.net/20.500.11754/21307http://www.sciencedirect.com/science/article/pii/S2211124714010675
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.12.038
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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