Respiratory Airway Secretory Cells in COPD

Maria C. Basil1, Fabian L. Cardenas-Diaz1, Jaymin J. Kathiriya2, Michael P. Morley1, Justine Carl1, Alexis N. Brumwell2, Jeremy Katzen1, Katherine J. Slovik1, Apoorva Babu3, Su Zhou1, Madison M. Kremp1, Katherine B. McCauley4, Shanru Li1, Joseph D. Planer1, Shah S. Hussain5, Xiaoming Liu6, Rebecca Windmueller7, Yun Ying1, Kathleen M. Stewart1, Michelle Oyster1, Jason D. Christie1, Joshua M. Diamond1, John F. Engelhardt6, Edward Cantu3, Steven M. Rowe5, Darrell N. Kotton4, Harold A. Chapman2, Edward E. Morrisey1
1Perelman School of Medicine, University of Pennsylvania, 2University of California, San Francisco, 3Penn-Children’s Hospital of Philadelphia Lung Biology Institute, 4Boston University, 5University of Alabama at Birmingham, 6University of Iowa, 7Children’s Hospital of Philadelphia, *Corresponding author
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Description The human lung differs substantially from its murine counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas exchange niche, forming an anatomical structure known as the respiratory bronchioles. Due to the lack of a murine counterpart, the cellular and molecular characterization of these respiratory bronchioles in the human lung remains an enigma. We show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modeling reveals that these respiratory airway secretory cells (RASCs) act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RASC lineage differentiation into AT2 cells is regulated by Notch and Wnt signaling. In COPD, RASCs are altered transcriptionally, corresponding to abnormal AT2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung not found in mouse that plays a critical role in maintaining the gas exchange compartment and is altered in chronic lung disease.
Dataset ID LMEX0000004405
Assay Type Single-cell RNA-seq
Organism Human
Stages Adult | 65+ years
Cell Count 154872
Technology 10x Genomics Chromium Single Cell Gene Expression
Reference Basil et al. (2022)
External databases GEO: GSE168191
FileDescriptionSize
Basil2022_COPD.h5adCOPD airway cells from the Basil 2022 cohort, peripheral region. 16,402 cells by 21,380 genes over 4 donors. obs carries the donor identifier and name, the library, the age, the sex, the GEO sample accession and the authors' own cell type. One of three objects this study serves; together they hold 47,808 of the study's 154,872 cells, the subset the authors released per condition and region.
Basil2022_healthy_distal.h5adControl airway cells from the Basil 2022 cohort, peripheral region. 15,769 cells by 22,164 genes over 5 donors. obs carries the donor identifier and name, the library, the age, the sex, the GEO sample accession and the authors' own cell type. One of three objects this study serves; together they hold 47,808 of the study's 154,872 cells, the subset the authors released per condition and region.
Basil2022_healthy_proximal.h5adControl airway cells from the Basil 2022 cohort, proximal region. 15,637 cells by 18,088 genes over 2 donors. obs carries the donor identifier and name, the library, the age, the sex, the GEO sample accession and the authors' own cell type. One of three objects this study serves; together they hold 47,808 of the study's 154,872 cells, the subset the authors released per condition and region.
LungMAP IDAlt IDSpeciesSexAgeAge GroupHealth Status
LMSPCOPDB0000001upenn_rasc_copd1Homo sapiensFemale66 years65+ yearsCOPD, peripheral
LMSPCOPDB0000002upenn_rasc_copd2Homo sapiensFemale69 years65+ yearsCOPD, peripheral
LMSPCOPDB0000003upenn_rasc_copd3Homo sapiensMale64 yearsAdultCOPD, peripheral
LMSPCOPDB0000004upenn_rasc_copd4Homo sapiensMale69 years65+ yearsCOPD, peripheral
LMSPCOPDB0000010upenn_rasc_donor1Homo sapiensMale52 yearsAdultControl, peripheral
LMSPCOPDB0000005upenn_rasc_donor2Homo sapiensFemale35 yearsAdultControl, peripheral
LMSPCOPDB0000006upenn_rasc_donor3Homo sapiensFemale76 years65+ yearsControl, peripheral/proximal
LMSPCOPDB0000008upenn_rasc_donor4Homo sapiensMale23 yearsAdultControl, peripheral
LMSPCOPDB0000009upenn_rasc_donor5Homo sapiensFemale29 yearsAdultControl, peripheral
LMSPCOPDB0000007upenn_rasc_donor6Homo sapiensMale54 yearsAdultControl, proximal