# Translational profiling of bladder sensory nerves and their cell type identities using dissociation free single nucleus sequencing

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $236,250

## Abstract

Abstract
Peripheral axons need sustained maintenance and repair to maintain connectivity with their targets. Local
axonal translation plays a role in regulation of protein and energy homeostasis across lifespan. The repertoire
of active mRNA translation during development and adulthood, and the ability to repair, regenerate and
translate specific subsets of mRNAs in relation to environmental cues is stored in distal axons. In many
instances these activities take place rapidly for immediate response at target sites before new transcripts
localize from the cell bodies. In disease states, altered axonal translation may affect elongation, withdrawal,
pruning, branching or survival. In the bladder innervation by afferent (sensory) and efferent (parasympathetic
and sympathetic) nerves is critical for its function. These nerves establish intricate connections with different
regions of the bladder and cell types including the urothelium, resident immune cells, smooth muscle cells and
blood vessels and likely employ local translation to maintain homeostasis and respond to injury or physiologic
changes. The identity of genes that are actively translated in bladder nerve terminal and subsequently their
role in bladder has not been studied. Defining actively translated mRNA in healthy and disease states in
bladder nerves and the identity of the soma source will provide insights into the mechanisms of
neuroanatomical and physiological interactions between the peripheral nervous and urinary systems, their
roles in a number of bladder diseases with neuronal basis and aid in rationally designing targeted therapies
aimed at preserving neuro-uro connections. This has potential to impact understanding of declining bladder
function in ageing, debilitating bladder symptoms and dysfunction (such as intractable pain, incontinence,
frequency and urgency to urinate) that affect millions of people in the US, neurodegenerative diseases and
neuropathies (diabetes, HIV) affecting bladder function. We will establish methods and proof of concept
studies to delineate the translatome in bladder sensory, autonomic axons in healthy male and female mice and
in female mice with UTI (Aim 1) and identify their cognate cell bodies by developing artifact –free single
nucleus RNA expression maps of DRG sensory neurons projecting to the bladder (Aim 2). The methods
developed will overcome challenges unique to composition, function and anatomy of bladder, its nerves and
corresponding soma that are different from the CNS or somatosensory system and serve as benchmark for
application to other lower urinary tract organs. The methods developed, genetic tools used and novel data
generated will be publicly shared for rapid adoption and accelerating studies to better understand regulation of
nerve terminals with their target sites by diverse set of users including basic and translational researchers,
computational biologists and clinicians interested in urinary tract disorders and normal physiolo...

## Key facts

- **NIH application ID:** 10309020
- **Project number:** 1R21DK128965-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sanjay Jain
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10309020

## Citation

> US National Institutes of Health, RePORTER application 10309020, Translational profiling of bladder sensory nerves and their cell type identities using dissociation free single nucleus sequencing (1R21DK128965-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10309020. Licensed CC0.

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