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| Status |
Public on Feb 15, 2022 |
| Title |
H3K27me3 conditions chemotolerance in triple-negative breast cancer [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Triple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes1. Residual disease, formed by cancer cells persistent to chemotherapy, remains the major clinical challenge towards full cure2,3. There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state4–6. Understanding non-genetic tumor evolution stands now as a prerequisite for the design of relevant combinatorial approaches to delay recurrence. Here we show that the repressive histone mark H3K27me3 is a determinant of cell fate under chemotherapy exposure, monitoring epigenomes, transcriptomes and lineage with single-cell resolution. We identify a reservoir of persister basal cells with EMT markers and activated TGF-β pathway leading to multiple chemoresistance phenotypes. We demonstrate that, in unchallenged cells, H3K27 methylation is a lock to the expression program of persister cells. Promoters are primed with both H3K4me3 and H3K27me3, and removing H3K27me3 is sufficient for their transcriptional activation. Leveraging lineage barcoding, we show that depleting H3K27me3 alters tumor cell fate under chemotherapy insult - a wider variety of tumor cells tolerate chemotherapy. Our results highlight how chromatin landscapes shape the potential of unchallenged cancer cells to respond to therapeutic stress and pave the way for combinatorial therapy with modulators of chromatin.
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| Overall design |
Single-cell RNA-seq of MDA-MB-468 Triple Negative Breast Cancer (TNBC) cell line in response to 5FU treatment in or without addition of GSKJ4 or UNC. Single-cell RNA-seq of HBCx95 Patient Derived Xenographt (PDX) of Triple Negative Breast Cancer (TNBC) in response to 5FU treatment (Capecitabine).
>>> Raw data not provided due to patient privacy concerns: GSM5017696-GSM5017700 and GSM5662564-GSM5662567. <<<
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| Contributor(s) |
Marsolier J, Prompsy P, Durand A, Vallot C |
| Citation(s) |
37340307 |
| |
| Submission date |
Jan 12, 2021 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Céline Vallot |
| E-mail(s) |
celine.vallot@curie.fr
|
| Phone |
0156246340
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| Organization name |
Institut Curie
|
| Street address |
26 Rue D'Ulm
|
| City |
Paris |
| ZIP/Postal code |
75005 |
| Country |
France |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE164716 |
H3K27me3 conditions chemotolerance in triple-negative breast cancer |
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| Relations |
| BioProject |
PRJNA691625 |
| SRA |
SRP301474 |
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