HCA Data Explorer

Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis.

Updated November 2, 2023

Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.

None
Paul A Reyfman1
James M Walter1
Nikita Joshi1
Kishore R Anekalla1
Alexandra C McQuattie-Pimentel1
Stephen Chiu1
Ramiro Fernandez1
Mahzad Akbarpour1
Ching-I Chen1
Ziyou Ren1
Rohan Verma1
Hiam Abdala-Valencia1
Kiwon Nam1
Monica Chi1
SeungHye Han1
Francisco J Gonzalez-Gonzalez1
Saul Soberanes1
Satoshi Watanabe1
Kinola J N Williams1
Annette S Flozak1
Trevor T Nicholson1
Vince K Morgan1
Deborah R Winter1
Monique Hinchcliff1
Cara L Hrusch2
Robert D Guzy2
Catherine A Bonham2
Anne I Sperling2
Remzi Bag2
Robert B Hamanaka2
Gökhan M Mutlu2
Anjana V Yeldandi1
Stacy A Marshall1
Ali Shilatifard1
Luis A N Amaral1
Harris Perlman1
Jacob I Sznajder1
A Christine Argento1
Colin T Gillespie1
Jane Dematte1
Manu Jain1
Benjamin D Singer1
Karen M Ridge1
Anna P Lam1
Ankit Bharat1
Sangeeta M Bhorade1
Cara J Gottardi1
G R Scott Budinger1
Alexander V Misharin1
1Northwestern University
2University of Chicago
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/daf9d982-7ce6-43f6-ab51-272577290606

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://github.com/NUPulmonary/Reyfman20182.https://www.nupulmonary.org/resources/?ds=fig1
GEO Series Accessions:
GSE121611, GSE122960

For information regarding data sharing and data use, please see our Data Access Policy.

Analysis Portals

UCSC Cell BrowserUCSC Cell Browser

Project Label

pulmonaryFibrosisPathobiology

Species

2 species

Sample Type

specimens

Anatomical Entity

lung

Organ Part

Unspecified

Selected Cell Types

Unspecified

Disease Status (Specimen)

6 disease statuses

Disease Status (Donor)

6 disease statuses

Development Stage

2 development stages

Library Construction Method

10x 3' v2

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

filtered_matrix_generation, raw_matrix_generation

File Format

5 file formats

Cell Count Estimate

76.1k

Donor Count

19
fastq.gz12 file(s)h538 file(s)mtx.gz2 file(s)tsv.gz4 file(s)xlsx1 file(s)