# Functional interrogation of a novel SCGB3A2+/SFTPB+ cell in the human airway

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $88,991

## Abstract

ABSTRACT
During a recent single cell RNA sequencing analysis of the developing human lung, we identified a cell
population characterized by a unique gene expression profile that has not previously been reported in the
human or mouse lung. These cells express SCGB3A2/SFTPB/CFTR, but lack markers for other well
characterized cell types such as club cells (SCGB1A1) or ionocytes (FOXI1). We refer to these as Fetal Airway
Secretory (FAS) cells given the expression of several secretory genes within the transcriptional signature.
Since nothing is known about FAS cells, and there is no analogous population in the murine lung, the
overarching goal of this proposal is to both describe these cells in detail, to interrogate their differentiation
potential, and to determine how these cells are regulated. By using an in vitro model of the developing human
lung epithelium called human Bud Tip Progenitor (BTP)-organoids, preliminary data shows that BTP-organoids
can give rise to both TP63+ progenitors and FAS cells during airway differentiation, and that this differentiation
can be modulated by TGFb/BMP/SMAD signaling. Single cell barcode-based lineage tracing during the
transition from BTP-to-airway suggest that clones of FAS cells or basal cells give rise to distinct subsets of
airway cells, with FAS cells giving rise to pulmonary neuroendocrine cells (PNECs) and a subset of C6+
multiciliated (MC) cells, while TP63+ progenitor cells give rise to secretory cells and MUC16+ MC cells. Based
on this data, we will test the overarching hypothesis that FAS cells differentiate distinct airway progenitor cell
that give rise to a subset of airway cell types. Given the novelty of this cell type, and the unique tools that we
have developed to assess the differentiating human epithelium in vitro, understanding this cell population will
provide foundational descriptive and mechanistic insights into human lung biology.

## Key facts

- **NIH application ID:** 11043879
- **Project number:** 3R01HL166139-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jason Spence
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $88,991
- **Award type:** 3
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11043879

## Citation

> US National Institutes of Health, RePORTER application 11043879, Functional interrogation of a novel SCGB3A2+/SFTPB+ cell in the human airway (3R01HL166139-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11043879. Licensed CC0.

---

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