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| Status |
Public on Jan 02, 2023 |
| Title |
Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform [2D and 3D] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD), the most common histological subtype, accounts for 40% of all cases. While existing genetically engineered mouse models (GEMMs) recapitulate the histological progression and transcriptional evolution of human LUAD, they are time-consuming and technically demanding. In contrast, cell line transplant models are fast and flexible, but these models fail to capture the full spectrum of disease progression. Organoid technologies provide a means to create next-generation cancer models that integrate the most advantageous features of autochthonous and transplant-based systems. However, robust and faithful LUAD organoid platforms are currently lacking. Here, we describe optimized conditions to continuously expand murine alveolar type 2 cells (AT2), a prominent cell-of-origin for LUAD, in organoid culture. These organoids display canonical features of AT2 cells, including marker gene expression, the presence of lamellar bodies, and an ability to differentiate into the AT1 lineage. We used this system to develop flexible and versatile immunocompetent organoid-based models of KRAS, BRAF, and ALK-mutant LUAD. Notably, organoid-based tumors display extensive burden and complete penetrance, and are histopathologically indistinguishable from their autochthonous counterparts. Altogether, this organoid platform is a powerful, versatile new model system to study LUAD.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for eGFP+/- cells.
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| Contributor(s) |
Naranjo S, Cabana CM, LaFave LM, Romero R, Shanahan SL, Bhutkar A, Westcott PM, Schenkel JM, Ghosh A, Liao LZ, Del Priore I, Yang D, Jacks T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Sep 22, 2022 |
| Last update date |
Jan 02, 2023 |
| Contact name |
A Bhutkar |
| Organization name |
MIT
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| Street address |
77 Massachusetts Avenue
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE213975 |
Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform |
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| Relations |
| BioProject |
PRJNA883399 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213974_SN_CC_RNAseq_2021_counts.xlsx |
1.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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