%0 Journal Article
%T High-resolution transcriptional dissection of in vivo Atoh1-mediated hair cell conversion in mature cochleae identifies Isl1 as a co-reprogramming factor
%A Celeste D. Rosencrance
%A Charles Gawad
%A David Finkelstein
%A Fei Zheng
%A Jian Zuo
%A John Easton
%A Ken Sugino
%A Robert Carter
%A Tetsuji Yamashita
%A Zoe Kellard
%J -
%D 2018
%R 10.1371/journal.pgen.1007552
%X In vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the conversion efficiency and producing functional target cells remain challenging. Ectopic Atoh1 expression in non-sensory supporting cells (SCs) in mouse cochleae induces their partial conversion to hair cells (HCs) at low efficiency. Here, we performed single-cell RNA sequencing of whole mouse sensory epithelia harvested at multiple time points after conditional overexpression of Atoh1. Pseudotemporal ordering revealed that converted HCs (cHCs) are present along a conversion continuum that correlates with both endogenous and exogenous Atoh1 expression. Bulk sequencing of isolated cell populations and single-cell qPCR confirmed 51 transcription factors, including Isl1, are differentially expressed among cHCs, SCs and HCs. In transgenic mice, co-overexpression of Atoh1 and Isl1 enhanced the HC conversion efficiency. Together, our study shows how high-resolution transcriptional profiling of direct cell conversion can identify co-reprogramming factors required for efficient conversion
%K Cochlea
%K Gene expression
%K Mouse models
%K Organ of Corti
%K Transcription factors
%K Principal component analysis
%K Mammalian genomics
%K RNA isolation
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007552