| First Author | Abernathy DG | Year | 2017 |
| Journal | Cell Stem Cell | Volume | 21 |
| Issue | 3 | Pages | 332-348.e9 |
| PubMed ID | 28886366 | Mgi Jnum | J:357902 |
| Mgi Id | MGI:6101314 | Doi | 10.1016/j.stem.2017.08.002 |
| Citation | Abernathy DG, et al. (2017) MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts. Cell Stem Cell 21(3):332-348.e9 |
| abstractText | Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9( *) and miR-124 (miR-9/9( *)-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9( *)-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show that ISL1 and LHX3 selectively drive conversion to a highly homogeneous population of human spinal cord motor neurons. This study shows that modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, providing a general platform for high-efficiency generation of distinct subtypes of human neurons. |
