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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2024 |
| Title |
Lineage-specific intolerance to oncogenic drivers restricts histological transformation [scRNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial cell types in the lung. Intriguingly, LUAD can histologically transform into SCLC following treatment with targeted therapies. Here we designed models to follow the conversion of LUAD to SCLC and found the barrier to histological transformation converges on tolerance to Myc, which we implicate as a lineage-specific driver of the pulmonary neuroendocrine cell. Histological transformations are frequently accompanied by activation of the Akt pathway. Manipulating this pathway permitted tolerance to Myc as an oncogenic driver, producing rare, stem-like cells, transcriptionally resembling the pulmonary basal lineage. These findings suggest histological transformation may require the plasticity inherent to the basal stem cell, enabling tolerance to previously incompatible oncogenic driver programs.
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| Overall design |
Single cell RNA sequencing was performed for 27 samples from genetically engineered mouse models. All samples were sorted from fresh, enzymatically dissociated lung tissues and, in most cases, triplicates were pooled before sequencing.
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| Contributor(s) |
Gardner EE, Earlie EM, Li K, Thomas J, Hubisz MJ, Stein BD, Zhang C, Cantley LC, Laughney AM, Varmus H |
| Citation(s) |
38330136 |
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| Submission date |
Nov 19, 2023 |
| Last update date |
Apr 02, 2024 |
| Contact name |
Ashley M Laughney |
| E-mail(s) |
ashley.laughney@gmail.com
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| Organization name |
Weill Cornell Medicine
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| Department |
Physiology, Biophysics, and Systems Biology
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| Lab |
Laughney Lab
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| Street address |
413 East 69th Street
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| City |
NEW YORK |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (27)
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| GSM7908319 |
Lung, de novo LUAD, rep 1 |
| GSM7908320 |
Lung, de novo LUAD, rep 2 |
| GSM7908321 |
Lung, de novo LUAD, rep 3 |
| GSM7908322 |
Lung, de novo SCLC, pooled |
| GSM7908323 |
Lung, de novo LUAD, pooled |
| GSM7908324 |
Lung, LUAD treated with osi, time1, pooled |
| GSM7908325 |
Lung, LUAD off DOX, time 1, pooled |
| GSM7908326 |
Lung, SCLC genotype, AT2 origin, pooled |
| GSM7908327 |
Lung, SCLC genotype, Pten loss, AT2 origin, time 1, pooled |
| GSM7908328 |
Lung, SCLC genotype, Pten loss, AT2 origin, time 2, pooled |
| GSM7908329 |
Lung, LUAD off DOX, time 2, pooled |
| GSM7908330 |
Lung, LUAD restarted on DOX, pooled |
| GSM7908331 |
Lung, LUAD off DOX, time 3, pooled |
| GSM7908332 |
Lung, de novo LUAD, Rb1 wt, pooled |
| GSM7908333 |
Lung, de novo LUAD, Rb1 wt, off DOX, pooled |
| GSM7908334 |
Lung, de novo LUAD, Myc wt, pooled |
| GSM7908335 |
Lung, Normal AT2, pooled |
| GSM7908336 |
Lung, Normal PNEC, pooled |
| GSM7908337 |
Lung, Normal AT2, Pten loss, pooled |
| GSM7908338 |
Lung, Normal AT2, Myc transgene, pooled |
| GSM7908339 |
Lung, Normal PNEC, Myc transgene, pooled |
| GSM7908340 |
Lung, Normal AT2, Pten loss, Myc transgene, pooled |
| GSM7908341 |
Lung, AT2, EGFR, Tp53 and Pten loss, pooled |
| GSM7908342 |
Lung, AT2, EGFR, Tp53 and Pten loss, Myc transgene, pooled |
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| This SubSeries is part of SuperSeries: |
| GSE248207 |
Lineage-specific intolerance to oncogenic drivers restricts histological transformation |
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| Relations |
| BioProject |
PRJNA1042807 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248202_Gardner_et-al-2023_processed_adata_TEC_merged_new_samples.h5ad.gz |
20.8 Gb |
(ftp)(http) |
H5AD |
| GSE248202_Gardner_et-al-2023_processed_adata_additional_Pten_samples.h5ad.gz |
225.7 Mb |
(ftp)(http) |
H5AD |
| GSE248202_Gardner_et-al-2023_processed_adata_atlas.h5ad.gz |
14.9 Gb |
(ftp)(http) |
H5AD |
| GSE248202_Gardner_et-al-2023_processed_adata_histological_transformation_subset.h5ad.gz |
2.2 Gb |
(ftp)(http) |
H5AD |
SRA Run Selector |
| Raw data are available in SRA |
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