PT  - JOURNAL ARTICLE
AU  - Kyle J. Travaglini
AU  - Ahmad N. Nabhan
AU  - Lolita Penland
AU  - Rahul Sinha
AU  - Astrid Gillich
AU  - Rene V. Sit
AU  - Stephen Chang
AU  - Stephanie D. Conley
AU  - Yasuo Mori
AU  - Jun Seita
AU  - Gerald J. Berry
AU  - Joseph B. Shrager
AU  - Ross J. Metzger
AU  - Christin S. Kuo
AU  - Norma Neff
AU  - Irving L. Weissman
AU  - Stephen R. Quake
AU  - Mark A. Krasnow
TI  - A molecular cell atlas of the human lung from single cell RNA sequencing
AID  - 10.1101/742320
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 742320
4099  - http://biorxiv.org/content/early/2020/03/20/742320.short
4100  - http://biorxiv.org/content/early/2020/03/20/742320.full
AB  - Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ∼75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution.