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| Status |
Public on May 22, 2021 |
| Title |
ASCL1 represses a latent osteogenic program in small cell lung cancer in multiple cells of origin [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
ASCL1 is a neuroendocrine-lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ~25% of human SCLC are ASCL1-low and associated with low-neuroendocrine fate and high MYC expression. Using genetically-engineered mouse models (GEMMs), we show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1+ state of SCLC in multiple cell types. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits tumor initiation, but surprisingly converts tumors to a SOX9+ mesenchymal/neural-crest-stem-like state that has the capacity to differentiate into RUNX2+bone tumors. ASCL1 represses SOX9 expression, as well as WNT and NOTCH developmental pathways, consistent with human gene expression data. SCLC demonstrates remarkable cell fate plasticity with ASCL1 repressing the emergence of non-endodermal stem-like fates that have the capacity for bone differentiation. Here, we perform ChIP on RPM tumors against ASCL1, NEUROD1, and H3k27Ac to view binding profiles and identify target genes of ASCL1 and NEUROD1.
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| Overall design |
Individual lung tumors from mice were micro-dissected, flash frozen and stored at -80°C until chromatin immunoprecipitation
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| Contributor(s) |
Olsen RR, Ireland AS, Oliver TG |
| Citation(s) |
34016693 |
| |
| Submission date |
Aug 04, 2020 |
| Last update date |
Sep 12, 2023 |
| Contact name |
Trudy Oliver |
| E-mail(s) |
[email protected], [email protected]
|
| 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) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE155692 |
ASCL1 represses a latent osteogenic program in small cell lung cancer in multiple cells of origin |
|
| Relations |
| BioProject |
PRJNA655228 |
| SRA |
SRP275831 |
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