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| Status |
Public on May 15, 2016 |
| Title |
Genome-wide chromatin landscape of chemical-induced neural stem cell reprogramming from defined fibroblasts |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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-driven approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging to develop. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine small molecules (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 towards 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 therefore provides an effective chemical approach for generating neural stem cells from mouse fibroblasts, and reveals mechanistic insights into underlying reprogramming process.
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| Overall design |
Genome-wide epigenetic changes of H3K4me1, H3K4me3, H3K27me3, and H3K27ac were analyzed by CHIP-seq for tdMEFs from day 0 (ciNSLC), day 4 (D4), day 8 (D8) of M9-induced neural reprogramming, and ciNSLCs and pri-NPC.
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| |
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| Contributor(s) |
Zhang M, Zheng J, Ding S |
| Citation(s) |
27133794 |
| |
| Submission date |
Mar 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Sheng Ding |
| Organization name |
THE J DAVID GLADSTONE INSTITUTES
|
| Department |
Gladstone Institute of Cardiovascular Disease
|
| Street address |
1650 Owens Street
|
| City |
SAN FRANCISCO |
| State/province |
California |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (25)
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| This SubSeries is part of SuperSeries: |
| GSE78978 |
CHIP-seq analysis for chemical-induced neural stem cells from defined fibroblasts |
|
| Relations |
| BioProject |
PRJNA314535 |
| SRA |
SRP071253 |
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