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| Status |
Public on Oct 12, 2018 |
| Title |
Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Breast cancer stem cells (BCSCs) are considered responsible for cancer relapse and drug-resistance. Understanding the identity of BCSCs may open new avenues in breast cancer therapy. Although several discoveries have been made on BCSCs characterization, the factors critical to BCSCs is largely unclear. This study was aimed to determine whether genomic mutation contributes to the acquisition of cancer stem-like phenotype, and to investigate the genetic and transcriptional features of BCSCs.
Methods: We detected the potential mutation hotspot regions by using whole genome sequencing on parental cancer cells and derived serial-generation spheroids in increasing order of BCSC frequency, and then performed target deep DNA sequencing in the level of bulk-cell and single-cell. To identify the transcriptional program associated with BCSCs, bulk-cell and single-cell RNA sequencing were performed.
Results: By analyzing whole genome sequencing of bulk cells, potential BCSCs associated mutation hotspot regions were detected. Validation by target deep sequencing, in both bulk-cell and single-cell levels, revealed no genetic changes specifically associated with BCSC phenotype. Moreover, single-cell RNA sequencing showed that cancer cells display profound transcriptional variability at the single-cell level that predicts BCSC features. Notably, this transcriptomic variability is enriched in transcription of a number of genes, revealed as BCSC markers. Individuals with breast cancer in a high-risk recurrence group exhibited higher expression of these transcriptomic variabilities, highlighting their clinical significance.
Conclusions: Transcriptional variability, not genetic mutations, distinguish BCSCs from non-BCSCs. The identified BCSCs markers can become novel targets for BCSCs.
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| Overall design |
To identify the transcriptional program associated with BCSCs, bulk-cell and single-cell RNA sequencing was performed on both spheroids and cells that cannot give rise to spheroid.
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| Contributor(s) |
Liu Q, Deng Z |
| Citation(s) |
30231942 |
| Submission date |
Jun 22, 2018 |
| Last update date |
Mar 20, 2019 |
| Contact name |
Meng ying Tong |
| Organization name |
Dalian Medical University
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| Street address |
Longtou Street
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| City |
Dalian |
| State/province |
Liaoning |
| ZIP/Postal code |
116041 |
| Country |
China |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA477551 |
| SRA |
SRP151150 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116180_All_FPKM_table.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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