RT Journal Article
SR Electronic
T1 Single-Cell Transcriptomic Analysis of Human Lung Reveals Complex Multicellular Changes During Pulmonary Fibrosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 296608
DO 10.1101/296608
A1 Paul A. Reyfman
A1 James M. Walter
A1 Nikita Joshi
A1 Kishore R. Anekalla
A1 Alexandra C. McQuattie-Pimentel
A1 Stephen Chiu
A1 Ramiro Fernandez
A1 Mahzad Akbarpour
A1 Ching-I Chen
A1 Ziyou Ren
A1 Rohan Verma
A1 Hiam Abdala-Valencia
A1 Kiwon Nam
A1 Monica Chi
A1 SeungHye Han
A1 Francisco J. Gonzalez-Gonzalez
A1 Saul Soberanes
A1 Satoshi Watanabe
A1 Kinola J.N. Williams
A1 Annette S Flozak
A1 Trevor T. Nicholson
A1 Vince K. Morgan
A1 Cara L. Hrusch
A1 Robert D. Guzy
A1 Catherine A. Bonham
A1 Anne I. Sperling
A1 Remzi Bag
A1 Robert B. Hamanaka
A1 Gökhan M. Mutlu
A1 Anjana V. Yeldandi
A1 Stacy A. Marshall
A1 Ali Shilatifard
A1 Luis A.N. Amaral
A1 Harris Perlman
A1 Jacob I. Sznajder
A1 Deborah R. Winter
A1 Monique Hinchcliff
A1 A. Christine Argento
A1 Colin T. Gillespie
A1 Jane D’Amico Dematte
A1 Manu Jain
A1 Benjamin D. Singer
A1 Karen M. Ridge
A1 Cara J. Gottardi
A1 Anna P. Lam
A1 Ankit Bharat
A1 Sangeeta M. Bhorade
A1 G.R. Scott Budinger
A1 Alexander V. Misharin
YR 2018
UL http://biorxiv.org/content/early/2018/04/06/296608.abstract
AB Pulmonary fibrosis is a devastating disorder that results in the progressive replacement of normal lung tissue with fibrotic scar. Available therapies slow disease progression, but most patients go on to die or require lung transplantation. Single-cell RNA-seq is a powerful tool that can reveal cellular identity via analysis of the transcriptome, but its ability to provide biologically or clinically meaningful insights in a disease context is largely unexplored. Accordingly, we performed single-cell RNA-seq on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and one bronchoscopic cryobiospy sample. Integrated single-cell transcriptomic analysis of donors and patients with pulmonary fibrosis identified the emergence of distinct populations of epithelial cells and macrophages that were common to all patients with lung fibrosis. Analysis of transcripts in the Wnt pathway suggested that within the same cell type, Wnt secretion and response are restricted to distinct non-overlapping cells, which was confirmed using in situ RNA hybridization. Single-cell RNA-seq revealed heterogeneity within alveolar macrophages from individual patients, which was confirmed by immunohistochemistry. These results support the feasibility of discovery-based approaches applying next generation sequencing technologies to clinically obtained samples with a goal of developing personalized therapies.One Sentence Summary Single-cell RNA-seq applied to tissue from diseased and donor lungs and a living patient with pulmonary fibrosis identifies cell type-specific disease-associated molecular pathways.