# SOX9 Expression Identifies A Novel Alveolar Stem Cell Population

> **NIH NIH F30** · DUKE UNIVERSITY · 2021 · $37,867

## Abstract

ABSTRACT
While the lung has long been known to undergo extensive regeneration during adulthood, the particular stem
cells involved in this process are only now being discovered. Recent studies have indicated that a subset of
alveolar Type II cells, a known stem cell population of the alveoli, are preferentially activated to proliferate
following different forms of injuries. Our preliminary data indicate that we have identified a novel stem cell
population located in the periphery of the adult mouse lung. These cells constitute a subset of Type II cells and
express SOX9, a transcription factor present in lung development but one whose expression had been previously
thought to subside by adulthood. Our preliminary data show that Sox9-lineage labeled cells expand, generating
new alveolar structures preferentially in the periphery of the lung lobes following partial left lobe pneumonectomy
in mice. Moreover, both Sox9+ and Sox9 negative cells upregulate and re-express SOX9 in 3-dimensional
organoid cultures, further suggesting that SOX9 functions to promote “stemness” in alveolar cells. Given these
findings, we hypothesize that Sox9+ cells are the primary alveolar stem cell, that they preferentially proliferate
to repopulate the homeostatic and post-pneumonectomy lung parenchyma, that they are necessary for these
processes, and that SOX9 enhances regenerative and differentiation potential of alveolar cells. We will address
these questions using a combination of lineage tracing, cell-type specific ablation, ex vivo assays, and RNA-
Sequencing approaches. Aim 1 will address the contribution of Sox9+ cells to both homeostasis and
compensatory lung growth following pneumonectomy. Aim 2 will determine whether Sox9+ cells are essential
for maintenance of alveolar homeostasis and injury repair. Aim 3 will address whether SOX9 expression can
substantially influence the stemness of alveolar Type II cells. Collectively, answering these questions will help
determine whether Sox9+ cells and/or SOX9 protein are viable therapeutic targets that will help accelerate lung
repair following acute injury.
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## Key facts

- **NIH application ID:** 10063551
- **Project number:** 5F30HL143911-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Arvind Konkimalla
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,867
- **Award type:** 5
- **Project period:** 2018-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063551

## Citation

> US National Institutes of Health, RePORTER application 10063551, SOX9 Expression Identifies A Novel Alveolar Stem Cell Population (5F30HL143911-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10063551. Licensed CC0.

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