# Investigating the role of mesenchymal R-Spondin2 during human lung development

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $45,324

## Abstract

PROJECT ABSTRACT
Mammalian respiratory system development is regulated by complex reciprocal signaling events that take
place between the epithelial cells lining the airways and the surrounding mesenchymal cells. Despite the lung
mesenchyme being home to cell types that provide crucial signals during development, the identity and
function of specific cell types in the lung mesenchyme are poorly defined, especially in the context of human
development. To interrogate mesenchymal cell heterogeneity in the developing human lung, our lab has
conducted single cell RNA sequencing on multiple human lung samples spanning 8-22 weeks of gestation.
Using cell-clustering approaches, we identified a mesenchymal cell population highly enriched for expression
of the WNT agonist R-Spondin2 (RSPO2). Strikingly, mutations in this gene cause severe lung aplasia in
humans. My co-fluorescent in situ hybridization (FISH) and immunofluorescence (IF) data from human lung
tissue sections show that RSPO2 is expressed adjacent to proliferating distal epithelial progenitor cells and
that the RSPO2 receptor, LGR5, is expressed almost exclusively in the epithelial progenitor cells. These data
suggest that RSPO2+ mesenchymal cells may have a critical role in regulating epithelial progenitor cells during
human lung development. The goals of this proposal are to: 1) interrogate mesenchymal cell heterogeneity and
function in the context of epithelial progenitor cell regulation in the developing human lung and 2) explain a
functional role for RSPO2+ mesenchymal cells during human lung development.

## Key facts

- **NIH application ID:** 9990315
- **Project number:** 1F31HL152531-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Renee Frances Conway
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,324
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990315

## Citation

> US National Institutes of Health, RePORTER application 9990315, Investigating the role of mesenchymal R-Spondin2 during human lung development (1F31HL152531-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990315. Licensed CC0.

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