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| Status |
Public on Dec 23, 2021 |
| Title |
LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. Purpose: To determine whether the restoration of Lkb1 drives changes in cell state and/or abundance within established oncogenic KRAS-driven lung tumors. Approach: To control LKB1 function in vivo, we generated an Lkb1XTR allele, which enables Cre-mediated disruption of Lkb1 expression during tumor development and subsequent FLPo-ERT2-mediated reactivation of Lkb1 within established tumors. Lung tumors were initiated in KT;Lkb1XTR/XTR (non-restorable) and KT;Lkb1XTR/XTR;FLPo-ERT2 (restorable) mice with Lenti-Cre. Following tumor development, lung tumor-bearing were treated with either corn oil vehicle or tamoxifen for two weeks prior to isolating total viable cells by FACS for single cell RNA-seq. Results: Lkb1 restoration did not result in any dramatic changes in the relative abundance of stromal cell types beyond a significant increase in a rare population of putative mast cells. There was a marked shift in the epithelial compartment from an indeterminate state to an alveolar type II epithelial-like identity in response to Lkb1 restoration. Conclusions: The acute transcriptional response to Lkb1 restoration is largely limited to the neoplastic epithelial compartment.
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| Overall design |
Lung tumors were initiated in KT;Lkb1XTR/XTR (non-restorable), and KT;Lkb1XTR/XTR;FLPo-ERT2 (restorable) mice with Lenti-Cre. Following tumor development and two weeks of treatment with either corn oil vehicle or tamoxifen, total viable cells FACS-isolated from lung tumors and subjected to single cell RNA-seq.
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| Contributor(s) |
Murray C, Winslow M |
| Citation(s) |
35228570 |
| |
| Submission date |
Jul 06, 2021 |
| Last update date |
Mar 24, 2022 |
| Contact name |
Christopher Murray |
| Organization name |
Stanford University
|
| Department |
Genetics
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| Lab |
Winslow
|
| Street address |
1291 Welch Rd. B261, Beckman Center
|
| City |
Stanford |
| State/province |
California |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE179560 |
LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer |
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| Relations |
| BioProject |
PRJNA744066 |
| SRA |
SRP327110 |
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