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Series GSE103354 Query DataSets for GSE103354
Status Public on Jul 30, 2018
Title A revised airway epithelial hierarchy includes CFTR-expressing ionocytes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Airways conduct gases to the lung and are disease sites of asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells by proximodistal location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq' , combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that characterize cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.
 
Overall design To understand normal tissue homeostasis, untreated cells were profiled using both 3'-droplet-based and full length plate-based single-cell RNAseq, in combination with genetic reporter-based lineage tracing.
 
Contributor(s) Montoro DT, Haber AL, Biton M, Vinarsky V, Chen S, Villoria J, Rogel N, Rao Tata P, Rowe SM, Engelhardt JF, Regev A, Rajagopal J, Lin B, Birket S, Yuan F, Leung H, Burgin G, Tsankov A, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Mou H, Shivaraju M, Bihler H, Mense M, Tearney G
Citation(s) 30069044
Submission date Aug 31, 2017
Last update date Jul 25, 2021
Contact name Adam Haber
E-mail(s) ahaber@hsph.harvard.edu
Organization name Harvard T. H. Chan School of Public Health
Street address 665 Huntington Ave, HSPH Building 1, Room 305
City Boston
State/province Massachusetts
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (325)
GSM2769083 Trachea epithelial single cell 1
GSM2769084 Trachea epithelial single cell 2
GSM2769085 Trachea epithelial single cell 3
Relations
BioProject PRJNA401883

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE103354_PulseSeq_UMI_counts.mtx.gz 402.8 Mb (ftp)(http) MTX
GSE103354_PulseSeq_UMI_counts.rds.gz 280.0 Mb (ftp)(http) RDS
GSE103354_RAW.tar 454.5 Mb (http)(custom) TAR (of MTX, TSV)
GSE103354_Trachea_droplet_UMIcounts.txt.gz 13.0 Mb (ftp)(http) TXT
GSE103354_Trachea_fullLength_TPM.txt.gz 4.8 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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