@article{26f6ffec87014ecd90e7c99e842b04c3,
title = "Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs",
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.",
keywords = "cell fate, chromatin regulation, direct conversion, epigenetics, microRNA, neuronal reprogramming, non-coding RNA, single-cell RNA-sequencing",
author = "Kitra Cates and McCoy, {Matthew J.} and Kwon, {Ji Sun} and Yangjian Liu and Abernathy, {Daniel G.} and Bo Zhang and Shaopeng Liu and Paul Gontarz and Kim, {Woo Kyung} and Shawei Chen and Wenjun Kong and Ho, {Joshua N.} and Burbach, {Kyle F.} and Gabel, {Harrison W.} and Morris, {Samantha A.} and Yoo, {Andrew S.}",
note = "Funding Information: We thank G. Dorn and V. Church for helpful suggestions on the manuscript. We thank the Genome Technology Access Center at Washington University School of Medicine for deep-sequencing experiments. We recognize BioRender.com for creation of the graphical abstract. This study was supported by the following programs, grants, and fellowships: Grass Fellowship in Neuroscience and the Interface of Psychology , Neuroscience and Genetics training fellowship ( T32GM081739 ) (M.J.M.), Cellular and Molecular Biology Training Program ( T32 GM007067 ) (K.C.), R01GM126112 (NIGMS), Paul G. Allen Frontiers Group , Vallee Foundation , and Alfred P. Sloan Foundation Awards (S.A.M.), NIH Director{\textquoteright}s Innovator Award ( DP2NS083372 ), Cure Alzheimer's Fund (CAF), Presidential Early Career Award for Scientists and Engineers ( PECASE ; 4DP2NS083372 ), RF1AG056296 ( NIA ), R01NS107488 ( NINDS ), Farrell Foundation Fund , and Mallinckrodt Scholar Award (A.S.Y.). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "7",
doi = "10.1016/j.stem.2020.08.015",
language = "English",
volume = "28",
pages = "127--140.e9",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "1",
}