期刊
CELL STEM CELL
卷 18, 期 5, 页码 653-667出版社
CELL PRESS
DOI: 10.1016/j.stem.2016.03.020
关键词
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资金
- California Institute for Regenerative Medicine
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Heart, Lung, and Blood Institute
- National Eye Institute/NIH
- Roddenberry Foundation
- William K. Bowes, Jr. Foundation
- Gladstone Institutes
- National Institute of Aging [AG048030]
Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes.
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