# iPSC-Derived Airway Basal Cells to Model Human Airway Development and Disease

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $411,032

## Abstract

Project Summary:
Our long-term objective is to improve our understanding of human lung development and disease using
iPSC directed differentiations to access cells from the same human being, at various stages of lung
development. Basal cells are epithelial stem/progenitor cells of the airway. They exhibit self-renewal and
multi-lineage differentiation in vitro and in vivo and can reconstitute the injured airway epithelium. Deriving
functional basal cells from induced pluripotent stem cells (iPSCs) would have broad ranging applications for
disease modeling, drug development, and potential cell-based therapies. The goal of this proposal is to (1)
identify for the first time the signaling pathways that control human airway BC specification, (2) determine
the in vitro conditions that support self-renewal and expansion of iPSC-derived BCs, (3) compare the
functional and transcriptional profile of these cells to bone-fide adult BCs, and (4) employ these engineered
cells to model the monogenic airway disease cystic fibrosis (CF). The central hypothesis is that precise
step-wise modulation of developmental pathways can be used to dissect the mechanisms of human basal
cell specification, maturation and differentiation and to model airway diseases. We present preliminary data
demonstrating the feasibility of deriving BCs from human iPSCs, including functional and single-cell RNA-
Seq (scRNA-Seq) characterizations. We introduce for the first time a novel human iPSC reporter line to
track and purify putative BCs. Based on mouse studies and our preliminary human data we hypothesize
that FGF and Hippo signaling play key roles in human BC specification and subsequent
maintenance/amplification of the progenitor pool. We propose a detailed comparison of iPSC-derived stem
cells to their in-vivo counterparts to establish their similarity but also harness the information to improve the
differentiation protocols for iPSCs.

## Key facts

- **NIH application ID:** 10240587
- **Project number:** 5R01HL139799-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Finn Hawkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,032
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240587

## Citation

> US National Institutes of Health, RePORTER application 10240587, iPSC-Derived Airway Basal Cells to Model Human Airway Development and Disease (5R01HL139799-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10240587. Licensed CC0.

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