Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing

Paul T Ranum; Alexander T Goodwin; Hidekane Yoshimura; Diana L Kolbe; William D Walls; Jin-Young Koh; David Z.Z He; Richard J.H Smith

doi:10.1016/j.celrep.2019.02.053

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Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing

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Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing

Paul T Ranum, Alexander T Goodwin, Hidekane Yoshimura, Diana L Kolbe, William D Walls, Jin-Young Koh, David Z.Z He and Richard J.H Smith

Cell reports (Cambridge), Vol.26(11), pp.3160-3171.e3

03/12/2019

DOI: 10.1016/j.celrep.2019.02.053

PMCID: PMC6424336

PMID: 30865901

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Abstract

Single-cell RNA sequencing is a powerful tool by which to characterize the transcriptional profile of low-abundance cell types, but its application to the inner ear has been hampered by the bony labyrinth, tissue sparsity, and difficulty dissociating the ultra-rare cells of the membranous cochlea. Herein, we present a method to isolate individual inner hair cells (IHCs), outer hair cells (OHCs), and Deiters’ cells (DCs) from the murine cochlea at any post-natal time point. We harvested more than 200 murine IHCs, OHCs, and DCs from post-natal days 15 (p15) to 228 (p228) and leveraged both short- and long-read single-cell RNA sequencing to profile transcript abundance and structure. Our results provide insights into the expression profiles of these cells and document an unappreciated complexity in isoform variety in deafness-associated genes. This refined view of transcription in the organ of Corti improves our understanding of the biology of hearing and deafness. [Display omitted] •Single-cell RNA-seq identifies inner and outer hair cell defining genes by AUC-ROC•Sorcin, a key component for cardiac excitation-contraction, is a top marker of OHCs•Analysis of deafness-associated genes identifies heretofore unrecognized exons•Nanopore long-read RNA-seq reveals splicing diversity and isoform abundance Single-cell RNA-seq of inner and outer auditory hair cells facilitates the identification of cell type-defining genes across a range of expression levels. Full-length reverse transcription with long-read sequencing identifies novel exons and unappreciated splicing diversity among deafness-associated genes.

Gene Expression

alternative splicing

auditory

cochlea

hair cells

hearing

isoforms

RNA sequencing

RNA-seq

scRNA-seq

single-cell RNA-seq

sorcin

splicing

Details

Title: Subtitle: Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing
Creators: Paul T Ranum - University of Iowa
Alexander T Goodwin - Roy J. and Lucille A. Carver College of Medicine
Hidekane Yoshimura - Shinshu University
Diana L Kolbe - University of Iowa
William D Walls - Roy J. and Lucille A. Carver College of Medicine
Jin-Young Koh - Roy J. and Lucille A. Carver College of Medicine
David Z.Z He - Creighton University
Richard J.H Smith - University of Iowa
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.26(11), pp.3160-3171.e3
Publisher: Elsevier Inc
DOI: 10.1016/j.celrep.2019.02.053
PMID: 30865901
PMCID: PMC6424336
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: DOI: 10.13039/100000055, name: NIDCD, award: DC003544, DC002842, DC012049
Language: English
Date published: 03/12/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984256929802771

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