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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 01, 2023 |
| Title |
Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing Kras induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD.
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| Overall design |
Normal lung alveolar type 2 cells and tumor cells of KP tumors were isolated from KP mouse model using flurescence-activated cell soring and analyzed by scRNAseq or bulk RNAseq.
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| Contributor(s) |
Li Z, Zhuang X, Pan C, Joost S, Torborg S, Tammela T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Oct 28, 2023 |
| Last update date |
Nov 01, 2023 |
| Contact name |
ZHUXUAN LI |
| E-mail(s) |
liz3@mskcc.org
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| Phone |
6467043994
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Cancer Biology and Genetics
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| Lab |
Tuomas Tammela
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| Street address |
417 E 68th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| GSM7869590 |
shKras,dox,20days |
| GSM7869591 |
KP,mrtx,5days |
| GSM7869592 |
KP,mrtx,20days |
| GSM7869593 |
shKras,dox,7days |
| GSM7869594 |
subq,MRTX,BFPneg |
| GSM7869595 |
subq,MRTX,BFPpos |
| GSM7869596 |
shKras,dox,3days,HTO |
| GSM7869597 |
shKras,dox,5days,HTO |
| GSM7869598 |
shKras,dox,10days,HTO |
| GSM7869599 |
shKras,dox,20days,HTO |
| GSM7869600 |
KP,mrtx,5days,HTO |
| GSM7869601 |
KP,mrtx,20days,HTO |
| GSM7869602 |
shKras,dox,7days,HTO |
| GSM7869603 |
subq,MRTX,BFPneg,HTO |
| GSM7869604 |
subq,MRTX,BFPpos,HTO |
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| This SubSeries is part of SuperSeries: |
| GSE246482 |
Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma |
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| Relations |
| BioProject |
PRJNA1033183 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246481_RAW.tar |
955.3 Mb |
(http)(custom) |
TAR (of CSV, H5, H5AD, MTX, TSV) |
| GSE246481_shKrasGEMM_norm_allgene.h5 |
1.6 Gb |
(ftp)(http) |
H5 |
SRA Run Selector |
| Raw data are available in SRA |
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