# Multi-modal characterization of three human lung niches at the single cell level

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $885,919

## Abstract

ABSTRACT
The respiratory system is architecturally complex and comprised of many compartments or niches responsible
for unique functions during respiration. While the human respiratory system exhibits a significant level of similarity
with rodents such as mice, it contains unique compartments and structures that are poorly understood but likely
to be important in understanding disease etiology and progression. As an example, the heterogeneity along the
proximal-distal axis of the human airway is significantly different than in the mouse, which may underlie the lack
of appropriate rodent models for many human lung diseases. This lack of understanding is similar for the human
pulmonary vasculature, where few animal models of diseases such as pulmonary hypertension exist. A detailed
analysis of these compartments and others in the developing human lung will result in the identification of new
cell lineages and molecular signatures of individual cells across the proximal-distal axis of the airways and along
the pulmonary vasculature. These data will need to be coupled with high resolution imaging techniques to build
a cellular atlas of the developing human lung. One of the major goals of Phase 2 of the LungMAP Consortium,
which was originally initiated in 2014, is to define the unique architectural, cell, and gene expression complexities
of the developing human lung using sophisticated and emerging technologies including single cell analytics.
Given the spatially specific architectural complexities of the human lung, we propose to focus on three important
compartments or niches: 1) the proximal airways, 2) the distal airways and alveolus including the terminal and
respiratory bronchioles (TBs and RBs), and 3) the pulmonary vasculature. We will utilize multi-modal genomic,
epigenomic, and proteomic techniques to define the cellular and molecular heterogeneity in these three niches
at the single cell level, and disseminate this information to allow investigators to extract cell-cell crosstalk that
defines and maintains these three niches in the developing human lung. Our group has developed and applied
novel genomic and imaging tools and designed interactive web applications to display and interrogate multi-
dimensional data that allows for specific, interactive, and continuous ongoing analysis of the data generated in
the LungMAP Consortium. Importantly, our group has demonstrated the ability to define cell-cell interactions
within specific lung niches by integrating genomic data with high resolution imaging. The ultimate goals of our
proposal are to 1) identify and map the cell lineages within three critical niches of the developing human
respiratory system, 2) define their spatial organization in relation to each other, 3) provide novel datasets to allow
researchers to identify the cell-cell interactions that are critical for their postnatal development, and 4) organize
and display the data for broad access throughout the scientific community using ...

## Key facts

- **NIH application ID:** 10447113
- **Project number:** 5U01HL148857-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** EDWARD E MORRISEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $885,919
- **Award type:** 5
- **Project period:** 2019-08-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447113

## Citation

> US National Institutes of Health, RePORTER application 10447113, Multi-modal characterization of three human lung niches at the single cell level (5U01HL148857-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447113. Licensed CC0.

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