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Series GSE123837 Query DataSets for GSE123837
Status Public on Feb 20, 2020
Title Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here we establish a robust method for identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA-sequencing and patient-derived xenograft (PDX) models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity, but micrometastases harbor a distinct transcriptome program conserved across PDX models that is highly predictive of poor survival in patients. Pathway analysis revealed mitochondrial oxidative phosphorylation (OXPHOS) as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of OXPHOS dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of OXPHOS in seeding and highlights its potential as a therapeutic target to prevent metastatic spread in breast cancer patients.
 
Overall design Analysis of single cell transcriptome changes between primary tumors and metastasis in mice PDX models of breast cancer.
 
Contributor(s) Lawson DA, Davis RT
Citation(s) 32144411
Submission date Dec 14, 2018
Last update date May 06, 2020
Contact name Devon A Lawson
E-mail(s) dalawson@uci.edu
Organization name UC Irvine
Department Physiology and Biophysics
Lab Lawson
Street address 839 Health Science Road, Sprague Hall 114
City Irvine
State/province CA
ZIP/Postal code 92697-3905
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (1707)
GSM3512239 HCI010_470_H_LU_1
GSM3512240 HCI010_470_H_LU_2
GSM3512241 HCI010_470_H_LU_3
Relations
BioProject PRJNA510105
SRA SRP173479

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE123837_HCI001_combinedmatrix.geneIDensemblID_FPKM_Submission.txt.gz 6.7 Mb (ftp)(http) TXT
GSE123837_HCI002_combinedmatrix.geneIDensemblID_FPKM_Submission.txt.gz 7.6 Mb (ftp)(http) TXT
GSE123837_HCI010_combinedmatrix.geneIDensemblID_FPKM_Submission.txt.gz 10.1 Mb (ftp)(http) TXT
GSE123837_RAW.tar 336.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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