Investigating the origin and functional properties of immune cells in noise-induced hearing loss

PROJECT SUMMARY/ABSTRACT
In this proposed work, we seek to understand the cellular identity of macrophages, the main immune cells in the
cochlea, in noise-induced hearing loss (NIHL). Our previous studies have shown that macrophages in the brain
have different developmental origins and their origin is associated with differences in their cellular identity and
functions depending on each disease condition. At present, the cellular identities and functional properties of
macrophages after noise damage are not well understood. Combining macrophage fate-mapping analysis with
single-cell RNA sequencing, our preliminary data revealed that cochlea macrophages during embryonic
development and in healthy adult are from two distinct origins. In-depth transcriptional analysis of cochlea
macrophages at single-cell resolution in steady state demonstrated the presence of several transcriptionally
distinct clusters of macrophages with specific biological functions. Based on this data and our previous work on
brain macrophages, we hypothesize that macrophages from different origins are involved in NIHL depending on
the age of the animal and stage of the disease (acute, recovery or recovered). Their distinct developmental origin
results in transcriptional diversity and differential responses to noise damage. Our findings will contribute to the
understanding of cochlea macrophage heterogeneity and functions in relation to their ontogeny after noise
damage. Defining the origins and differential gene expression and functions of cochlea macrophage populations
will help us to refine our understanding of the role of these cells in different stage after noise damage and enable
us to design new molecular and cellular therapies based on targeting inflammation.
Specific Aim 1: Identifying the cellular origin of cochlea macrophages in young adult and aged mice exposed
to noise damage.
Specific Aim 2: Identifying mechanisms by which macrophages contribute to NIHL through single-cell RNA
sequencing of macrophage populations present in cochlea.

Grant Number: 5R21DC021275-03
NIH Institute/Center: NIH
Principal Investigator: Bahareh Ajami