Single-cell RNA-sequencing of stria vascularis cells in the adult Slc26a4 mouse.

Background: The primary pathological alterations of Pendred syndrome are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular contributions of specific cell types remain poorly characterized. Therefore, we aimed to identify pH regulators in pendrin-expressing cells that may contribute to the homeostasis of endolymph pH and define the cellular pathogenic mechanisms that contribute to the dysregulation of cochlear endolymph pH in Slc26a4 mice.

Mutation-agnostic RNA interference with engineered replacement rescues -related hearing loss.

Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations in , a gene encoding the pore-forming subunit of the hair cell mechanotransduction channel, cause DFNA36 and DFNB7/11, respectively, accounting for ∼2% of genetic hearing loss. Previous work has established the efficacy of mutation-targeted RNAi in treatment of murine models of autosomal dominant non-syndromic deafness.

De novo variants are a common cause of genetic hearing loss.

Purpose: De novo variants (DNVs) are a well-recognized cause of genetic disorders. The contribution of DNVs to hearing loss (HL) is poorly characterized. We aimed to evaluate the rate of DNVs in HL-associated genes and assess their contribution to HL.

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

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.

CNV-ROC: A cost effective, computer-aided analytical performance evaluator of chromosomal microarrays.

Chromosomal microarrays (CMAs) are routinely used in both research and clinical laboratories; yet, little attention has been given to the estimation of genome-wide true and false negatives during the assessment of these assays and how such information could be used to calibrate various algorithmic metrics to improve performance. Low-throughput, locus-specific methods such as fluorescence in situ hybridization (FISH), quantitative PCR (qPCR), or multiplex ligation-dependent probe amplification (MLPA) preclude rigorous calibration of various metrics used by copy number variant (CNV) detection algorithms. To aid this task, we have established a comparative methodology, CNV-ROC, which is capable of performing a high throughput, low cost, analysis of CMAs that takes into consideration genome-wide true and false negatives.