# Regulation of Lineage Plasticity and Acinar Regeneration in Adult Salivary Glands

> **NIH NIH R21** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $235,887

## Abstract

Project Summary/Abstract:
Loss of salivary gland function severely affects patient’s oral health and overall quality of life. Restoration of
secretory units and gland function through promoting endogenous healing and regeneration of
acinar cells may offer an effective and non-invasive treatment option for patient with salivary dysfunction.
By combining genetic lineage tracing approaches with a classic model of severe and reversible glandular injury
in the adult mouse submandibular gland, we have interrogated the capacity of diverse parenchymal cell
populations to undergo lineage reprogramming toward secretory acinar cells. Our data revealed that following
substantial loss of acinar cells, not only ductal stem cells but differentiated cell populations including
myoepithelial and ductal cells serve as reserve acinar progenitors and contribute to more than 90% of
regenerated acini. We found that plasticity of myoepithelial and cKit+ duct cells that involves reversion into a
bipotent progenitor-like state before re-differentiation to proacinar/acinar cells is the major mechanism of acinar
regeneration in this model of injury. These novel findings provide the first direct evidence for plasticity of
diverse epithelial cells toward saliva-secreting acinar cells; and build the foundation for a clear operational
understanding of the molecular mechanisms that could be harnessed to induce endogenous regeneration
of acini in the degenerative salivary glands. What triggers this broad lineage plasticity in epithelial cells and
how these cells reprogram their fate and acquire proliferative and bi-lineage differentiation capacity is currently
unknown. We hypothesize that cues from the wound environment provoke lineage plasticity in diverse epithelial
cell populations toward acinar cells. To test this hypothesis we will use our established transgenic mouse models
and two models of mild and severe obstruction-induced injury to characterize inflammatory and stromal
components that are specific to a pro-plastic microenvironment and then functionally assess the role of these
components on promoting de novo formation of acini (Aim 1). We then take a systematic approach to decipher
the unique and common molecular signature of myoepithelial cells and ductal cells as they undergo lineage
reversion, and gain valuable insights into reprogramming of these two relatively abundant cell populations into
acinar cells (Aim 2). This exploratory/developmental R21 proposal will yield important information that can be
used as a foundation for developing effective targeted strategies for endogenous regeneration of acinar cells in
damaged, degenerative or aging salivary glands, an important therapy for a large patient population suffering
from hyposalivation and may also identify gatekeepers of epithelial differentiation that inhibit progenitor-like
traits under normal condition.

## Key facts

- **NIH application ID:** 10353421
- **Project number:** 5R21DE030653-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** SOOSAN GHAZIZADEH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,887
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353421

## Citation

> US National Institutes of Health, RePORTER application 10353421, Regulation of Lineage Plasticity and Acinar Regeneration in Adult Salivary Glands (5R21DE030653-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10353421. Licensed CC0.

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