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Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs
- Source :
- Cell stem cell. 28(1)
- Publication Year :
- 2019
-
Abstract
- Cell-fate conversion generally requires reprogramming effectors to both introduce fate programs of the target cell type and erase the identity of starting cell population. Here, we reveal insights into the activity of microRNAs miR-9/9∗ and miR-124 (miR-9/9∗-124) as reprogramming agents that orchestrate direct conversion of human fibroblasts into motor neurons by first eradicating fibroblast identity and promoting uniform transition to a neuronal state in sequence. We identify KLF-family transcription factors as direct target genes for miR-9/9∗-124 and show their repression is critical for erasing fibroblast fate. Subsequent gain of neuronal identity requires upregulation of a small nuclear RNA, RN7SK, which induces accessibilities of chromatin regions and neuronal gene activation to push cells to a neuronal state. Our study defines deterministic components in the microRNA-mediated reprogramming cascade.
- Subjects :
- Population
Cell fate determination
Biology
03 medical and health sciences
0302 clinical medicine
Genetics
Humans
Epigenetics
education
Transcription factor
030304 developmental biology
Regulation of gene expression
0303 health sciences
education.field_of_study
Cell Differentiation
Cell Biology
Fibroblasts
Non-coding RNA
Cellular Reprogramming
Chromatin
Cell biology
MicroRNAs
Molecular Medicine
Reprogramming
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 18759777
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell stem cell
- Accession number :
- edsair.doi.dedup.....c05e6f4028dc05afea485c8b22202b13