# Regulation of mesenchymal cells by epithelial Wnt ligands

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $608,155

## Abstract

PROJECT SUMMARY
Alveologenesis requires co-development of the epithelium, mesenchyme, and vasculature, the failure of which
is a cardinal feature of bronchopulmonary dysplasia (BPD). This process depends on precisely controlled
intercellular signaling, such as Fgf, Pdgf, Shh, and Vegf signaling, as revealed by recent work including ours in
the previous grant period. Another major signaling pathway, Wnt signaling, extensively studied in embryonic
lungs and potentially involved in adult lungs, is poorly understood in the neonatal period. Moreover, published
Wnt studies focus on epithelial cells, but largely ignore the robust expression of Wnt target genes within the
postnatal mesenchyme. Further contributing to our limited understanding of mesenchymal Wnt signaling is lack
of clarity on the cell types in the mesenchyme, which starts to be unveiled via single-cell genomics. By
following the unexpected signaling role of AT1 cells in the previous grant period, we have obtained evidence
that epithelial WNT ligands specifically signal toward myofibroblasts during alveologenesis. Pursuing, as
proposed, the signaling cells (Aim 1), the receiving cells (Aim 2), and the disease relevance (Aim 3) is
expected to not only elucidate the little-known mesenchymal Wnt signaling, but also establish an experimental
paradigm applicable to future lung mesenchyme research.

## Key facts

- **NIH application ID:** 10122223
- **Project number:** 2R01HL130129-06
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jichao Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $608,155
- **Award type:** 2
- **Project period:** 2016-03-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122223

## Citation

> US National Institutes of Health, RePORTER application 10122223, Regulation of mesenchymal cells by epithelial Wnt ligands (2R01HL130129-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10122223. Licensed CC0.

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