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Series GSE246368 Query DataSets for GSE246368
Status Public on Oct 26, 2023
Title A map of signaling responses in human airway epithelium
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Receptor-mediated signaling plays a central role in tissue regeneration, and it is dysregulated in disease. Here, we build a signaling–response map for a model regenerative human tissue: the airway epithelium. We analyzed the effect of 17 receptor-mediated signaling pathways on organotypic cultures to determine changes in abundance and phenotype of all epithelial cell types. This map recapitulates the gamut of known airway epithelial signaling responses to these pathways. It defines convergent states induced by multiple ligands and diverse, ligand-specific responses in basal-cell and secretory-cell metaplasia. We show that loss of canonical differentiation induced by multiple pathways is associated with cell cycle arrest, but that arrest is not sufficient to block differentiation. Using the signaling-response map, we show that a TGFB1-mediated response underlies specific aberrant cells found in multiple lung diseases and identify interferon responses in COVID-19 patient samples. Thus, we offer a framework enabling systematic evaluation of tissue signaling responses.
 
Overall design Human bronchial epithelial cells were cultured at air-liquid interface (ALI) without treatment to drive differentiation into a pseudo- stratified epithelium that recapitulates the physiological cell types of the airway. The differentiated luminal cells were then stripped through calcium depletion, leaving the remaining basal cells to regenerate the tissue. This was done in the presence of a signaling agonist added to each well at a dosage 10- to 100-fold greater than the IC50. One condition was kept unperturbed for control. After 2 weeks of differentiation, the final composition of the tissue was analyzed by scRNA-Seq and imaging. Cells were run in two separate experiments: donor #429581 was collected individually; donors #221175 and #323353 were pooled and captured simultaneously, except for one condition (ActA) for which we only collected donor #323353. We call these two experiments as ali12 and ali13 respectively in the metadata files.
Web link https://www.cell.com/cell-systems/pdf/S2405-4712(24)00059-0.pdf
 
Contributor(s) Kukreja K, Mccauley KB, Jaffe AB, Klein AM
Citation(s) 36597531
Submission date Oct 26, 2023
Last update date Jun 08, 2024
Contact name Kalki Kukreja
E-mail(s) kukreja.kalki@gmail.com
Phone 6179550582
Organization name Harvard University
Street address 200 Longwood Avenue
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (2)
GSM7867718 hBEC, signaling perturbations, donor no. 429581 [ali12]
GSM7867719 hBEC, signaling perturbations, pooled donors no. 221175 and 323353 [ali13]
Relations
BioProject PRJNA1032611

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
GSE246368_RAW.tar 187.6 Mb (http)(custom) TAR (of CSV, TSV)
GSE246368_ali12.yaml.gz 1.1 Kb (ftp)(http) YAML
GSE246368_ali13.yaml.gz 1.3 Kb (ftp)(http) YAML
GSE246368_all_data.h5ad.gz 242.1 Mb (ftp)(http) H5AD
GSE246368_sample_information.txt.gz 1.3 Kb (ftp)(http) TXT
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Raw data are available in SRA

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