# The role of lung lipofibroblasts in alveolar differentiation

> **NIH NIH R21** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $233,250

## Abstract

Abstract
A complication of preterm birth is underdeveloped lungs that lack surfactant and adequate gas
exchange due to immature alveoli. Although recent advances have been made, the process of
alveolar maturation is not well understood. A goal of this project is to understand signaling
from mesenchymal cells that direct alveologenesis, the final stage of lung development. We
have found that disruption of a specialized fibroblast, the lipofibroblast, results in reduced type
II alveolar cell differentiation. Type II alveolar cells are responsible for surfactant production,
and we will investigate the communication between lipofibroblasts and alveolar cells during lung
development in the mouse. The lipofibroblast has been a difficult cell to identify, and little is
known about the function of these cells. Our preliminary data demonstrate that a transcription
factor is required for the development of lipofibroblasts and alveolar differentiation. Based upon
these preliminary findings, we hypothesize that lipofibroblasts are required for the later steps of
lung development and that they secrete growth factors that are required specifically for terminal
differentiation of type II alveolar cells. We will investigate these cellular interactions in two
specific aims. In specific aim I, we will determine how lipofibroblasts impact alveolar
differentiation by examining the temporal requirement for lipofibroblasts and by evaluating
postnatal lung development in mice lacking lipofibroblasts. In Specific Aim II we will use in
vitro organoid culture and gene expression profiling to explore the lipofibroblast cellular signals
that direct type II alveolar differentiation. Together these aims will define the role of the
lipofibroblast and potentially identify therapeutic targets for increasing the rate of type II alveolar
differentiation in preterm births.

## Key facts

- **NIH application ID:** 10331843
- **Project number:** 5R21HL156112-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Michelle D Tallquist
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $233,250
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331843

## Citation

> US National Institutes of Health, RePORTER application 10331843, The role of lung lipofibroblasts in alveolar differentiation (5R21HL156112-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331843. Licensed CC0.

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