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Series GSE81383 Query DataSets for GSE81383
Status Public on Jan 12, 2017
Title Mapping heterogeneity in a patient-derived melanoma culture by single-cell RNA-seq
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy.
 
Overall design RNA-seq of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively.
 
Contributor(s) Gerber T, Willscher E, Loeffler-Wirth H, Hopp L, Schadendorf D, Schartl M, Anderegg U, Camp G, Treutlein B, Binder H, Kunz M
Citation(s) 27903987, 29614062
Submission date May 12, 2016
Last update date May 21, 2019
Contact name Edith Willscher
E-mail(s) willscher@izbi.uni-leipzig.de
Organization name IZBI
Street address Haertelstra├če 16-18
City Leipzig
ZIP/Postal code 04107
Country Germany
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (307)
GSM2151479 A1_mel
GSM2151480 A2_mel
GSM2151481 A3_mel
Relations
BioProject PRJNA321420
SRA SRP074894

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
GSE81383_data_melanoma_scRNAseq_BT_2015-07-02.txt.gz 3.8 Mb (ftp)(http) TXT
GSE81383_data_melanoma_scRNAseq_BT_Mel.txt.gz 7.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data is available on Series record

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