|
| Status |
Public on May 28, 2020 |
| Title |
MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [Single Cell RNA seq on RPM time-series cells and 4 RPM bulk tumors] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of lineage-related transcription factors: ASCL1, NEUROD1, POU2F3 or YAP1, but their origins remain unknown. Here, we develop an in vitro model of MYC-driven SCLC tumor cell progression and perform a time-series analysis of single-cell transcriptome profiling to reveal that MYC drives the dynamic evolution of SCLC subtypes. Analyses of these single-cell RNA seq data reveal that MYC promotes a temporal shift from an Ascl1-to-Neurod1-to-Yap1+ state from a neuroendocrine cell of origin. They also support our findings that MYC activates Notch signaling to dedifferentiate tumor cells to non-neuroendocrine fates. Additional single-cell RNA sequencing of 4 bulk Rb1/Trp53/MycT58A (RPM) tumors reveal individual tumors to consist of cells at nearly every stage of RPM tumor evolution modeled in vitro. Together, these single-cell RNA sequencing data place 3 of 4 SCLC subtypes on a defined trajectory and suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.
|
| |
|
| Overall design |
Live RPM time-series transition cells underwent library preparation directly from cell culture at days 4 (n = 2 of the same sample), 7, 11, 14, 17, and 21 post-digestion for a total of 6 distinct transition timepoints. Additionally, we performed single-cell RNA sequencing of 4 bulk RPM tumors.
|
| |
|
| Contributor(s) |
Ireland AS, Oliver TG |
| Citation(s) |
34016693 |
| |
| Submission date |
Apr 23, 2020 |
| Last update date |
Sep 12, 2023 |
| Contact name |
Trudy Oliver |
| E-mail(s) |
tgo@duke.edu, trudy.oliver@duke.edu
|
| Phone |
6174607487
|
| Organization name |
Duke University
|
| Department |
Pharmacology & Cancer Biology
|
| Lab |
theoliverlab
|
| Street address |
Duke University, Box 3813, LSRC Room C138B, 308 Research Drive
|
| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27708 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (11)
|
|
| This SubSeries is part of SuperSeries: |
| GSE149180 |
MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [SuperSeries] |
|
| Relations |
| BioProject |
PRJNA627598 |
| SRA |
SRP258037 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149179_Filtered_TimeCourse_barcodes.tsv.gz |
83.1 Kb |
(ftp)(http) |
TSV |
| GSE149179_Filtered_TimeCourse_features.tsv.gz |
248.7 Kb |
(ftp)(http) |
TSV |
| GSE149179_Filtered_TimeCourse_matrix.mtx.gz |
213.0 Mb |
(ftp)(http) |
MTX |
| GSE149179_RPM1_barcodes.tsv.gz |
27.6 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM1_features.tsv.gz |
277.4 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM1_matrix.mtx.gz |
48.5 Mb |
(ftp)(http) |
MTX |
| GSE149179_RPM2_barcodes.tsv.gz |
15.8 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM2_features.tsv.gz |
277.4 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM2_matrix.mtx.gz |
18.8 Mb |
(ftp)(http) |
MTX |
| GSE149179_RPM3_barcodes.tsv.gz |
5.7 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM3_features.tsv.gz |
277.4 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM3_matrix.mtx.gz |
6.2 Mb |
(ftp)(http) |
MTX |
| GSE149179_RPM4_barcodes.tsv.gz |
11.6 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM4_features.tsv.gz |
277.4 Kb |
(ftp)(http) |
TSV |
| GSE149179_RPM4_matrix.mtx.gz |
15.3 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...