# Alternative splicing in the mouse inner ear at single cell resolution

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $218,750

## Abstract

Sensorineural hearing loss and vestibular dysfunction are common sensory disorders affecting 
millions of
individuals worldwide¹,². The primary cause of both hearing loss and peripheral vestibular 
disorders in humans is dysfunction of the inner ear, which can occur as a result of noise exposure, 
aging, genetic defects, environmental exposure to pathogens, and as a side effect of ototoxic 
medications. There are limited therapies for sensorineural hearing loss and vestibular dysfunction, 
mainly due to the lack of understanding of some of the molecular mechanisms that govern the hearing 
and balance organs. There remain key unanswered questions about the genetic architecture and 
molecular mechanisms of transcriptional control used during mammalian development and within the 
adult inner ear. Recently, single cell RNA sequencing technology has shown the remarkable 
transcriptional heterogeneity of cell types and developmental dynamics of the mouse inner ear³??. 
However, transcriptional diversity and control is only one level of genetic regulation. One of the 
key underlying mechanisms of transcriptomic and protein diversity is through alternative splicing. 
Cells use alternative splicing to diversify their number of proteins, change translation 
efficiency, control transcript localization, and make non-coding RNAs?,?. Only a limited number of 
genes that undergo alternative splicing have been identified in the inner ear at cell type 
resolution?. Understanding alternative splicing of genes at the single cell level is critically 
important as any future therapies targeting a specific gene may have on/off target effects in 
different subsets of cells. We hypothesize that there is cell type-specific diversity of 
alternatively spliced mRNA within the mammalian inner ear. Moreover, regulation of alternative 
splicing events occurs through specific RNA binding proteins (RBPs). We will test this hypothesis 
through two aims: Aim 1 is to characterize the transcriptome-wide alternative splicing landscape of 
the mouse inner ear at single cell resolution. Using newly developed computational tools, we will 
identify alternatively spliced genes within both the developing and adult mouse inner ear for the 
entire transcriptome. Aim 2 will determine the role of RNA binding proteins in regulating 
alternative splicing programs in the inner ear at single cell resolution. Regulation of alternative 
splicing events is a key post-transcriptional mechanism that cells use to determine what splicing 
program mRNA goes through as carried out by RNA binding proteins. We will characterize the 
expression of RBPs within the developing mouse inner ear and link this to alternative splicing 
through computational and validation techniques to develop a spatial and temporal map of 
alternative splicing programs. In sum, we will define the heterogeneity of cell types based on 
single cell isoform-level data during development and in the adult mammalian inner ear, and we will...

## Key facts

- **NIH application ID:** 10975182
- **Project number:** 1R21DC022058-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Taha A Jan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,750
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975182

## Citation

> US National Institutes of Health, RePORTER application 10975182, Alternative splicing in the mouse inner ear at single cell resolution (1R21DC022058-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10975182. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*