# Interferon-mediated in vitro and in vivo Regulation of Airway Progenitor Cells in Regeneration of Functional Alveoli

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $53,547

## Abstract

PROJECT SUMMARY
Recapitulation of normal lung function following a severe acute injury implies an inherent capability of lung to
regenerate but the sources and relative regenerative capacities of lung epithelial stem/progenitor cells remain
unclear. Although virtually all differentiated epithelial lineages can re-enter the cell cycle, increasing evidence
indicates that subpopulations of distal airway cells may be particularly robust in their capacity to expand, migrate,
and reconstitute alveolar barriers. Recent studies from our lab have uncovered Sox2pos/p63neg epithelial
progenitors (EPs) with regenerative potential and ability to differentiate towards alveolar fate. Further, numerous
other studies have described a fraction of Scgb1a1-labeled cells to also have in vitro and in vivo regenerative
capacity. However, their exact identities, location, and regulation remains unclear. To further define the EPs, we
performed large scale single cell sequencing of flow-sorted lung epithelial cells enriched in EPs, which identified
a quiescent EP population. These cells, with a transcriptomic similarity to embryonic Sox9pos lung bud cells, have
increased expression of interferon (IFN)-regulated genes. Interestingly, these cells also express a number of
genes associated with cell cycle and key cyclin inhibitors Cdkn1a (p21) and Cdkn1c (p57), suggestive of their
ability to proliferate under favorable conditions. Indeed, IFNpos cells represent the regenerative fraction of the
airway epithelium (including that of Scgb1a1-labeled cells) in various in vitro conditions tested. Importantly, these
cells also have the ability to differentiate towards either basal (marked by Cytokeratin 5 expression) or alveolar
(marked by surfactant protein C expression) cells. Thus, my preliminary data have identified the regenerative
fraction of the airway epithelium. However, their regulation in vivo and their ability to functionally contribute to
lung epithelial regeneration post injury remain unknown. To this end, we hypothesize that low levels of
constitutive IFN signaling regulates and maintains a pool of rare airway EPs that mobilize to regenerate
alveolar epithelium following injury. We will test this hypothesis in following two aims: 1) To determine the
role of IFN signaling in maintenance of quiescent p63neg EPs in uninjured mouse lung. 2) Determine the role of
IFN signaling in in vivo responses of p63neg EPs following major injury. We will leverage mouse models to
abrogate active IFN signaling in injured mice to study its role in maintenance of EPs. Likewise, conditional airway
epithelial deletion of Stat1 followed by injury will determine the role of IFN/Stat1 signaling in injury response.
Finally, exogenously expanded EPs will be transplanted in injured lungs and functional recovery will be measured
by oxygenation and lung function. This project has a significant potential to clarify the signaling pathways
regulating lung epithelial progenitor cell response during qui...

## Key facts

- **NIH application ID:** 9925055
- **Project number:** 5F32HL143931-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jaymin J Kathiriya
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,547
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925055

## Citation

> US National Institutes of Health, RePORTER application 9925055, Interferon-mediated in vitro and in vivo Regulation of Airway Progenitor Cells in Regeneration of Functional Alveoli (5F32HL143931-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9925055. Licensed CC0.

---

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