# Identifying and characterizing human pulmonary neuroendocrine stem cells and their diversity

> **NIH NIH R56** · STANFORD UNIVERSITY · 2024 · $752,555

## Abstract

PROJECT SUMMARY
Pulmonary neuroendocrine cells (PNECs) are sensory epithelial cells that signal to the brain
through sensory neurons and locally through neuropeptides and neurotransmitters. We used
scRNA-seq to comprehensively profile and analyze mouse and human PNECs, which revealed
over 40 PNEC neuropeptides and hormones in diverse combinations. Here, we propose to map
the innervation and molecular subtypes of human pulmonary neuroendocrine cells and identify
the functional subsets in human lung, beginning with an investigation of functionally distinct
neuroendocrine stem cells. Using precision cut lung slice cultures to establish an injury model
inducing proliferation, we will identify the location of proliferative PNECs and measure their
complete transcriptomic profiles by scRNA-seq. In parallel, we will use multiplex single molecule
in situ hybridization methods to localize the human PNEC neuropeptides, identify their
combinations in situ, and their cognate receptors in human lung. Collectively, these studies will
comprehensively characterize the cellular and molecular features of human PNECs, their stem
cells and niches. PNEC expansions and ectopic pulmonary neuroendocrine cells are the
distinguishing pathologic features underlying a common form of pediatric diffuse lung disease,
neuroendocrine cell hyperplasia of infancy (NEHI), which is characterized by diffuse obstructive
ventilatory defect. In adults, a pre-neoplastic condition called diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia (DIPNECH) is also associated with airway obstruction and
prominent respiratory symptoms thought to be due to bioactive peptides from neuroendocrine
cells. We will identify the neuropeptide and receptor expression in pathological cell niches
during NE stem cell transformation in DIPNECH. This work establishes a molecular foundation
for the diverse clinical presentations associated with pulmonary neuroendocrine lesions and
identifies panels of neuropeptides and hormones localized to precise anatomic locations that will
provide the basis for developing novel diagnostic and therapeutic approaches.

## Key facts

- **NIH application ID:** 11192953
- **Project number:** 1R56HL172049-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Christin Sucheng Kuo
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $752,555
- **Award type:** 1
- **Project period:** 2024-09-24 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11192953

## Citation

> US National Institutes of Health, RePORTER application 11192953, Identifying and characterizing human pulmonary neuroendocrine stem cells and their diversity (1R56HL172049-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11192953. Licensed CC0.

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