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Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder.

Oncotarget | 2016

Cell-to-cell expression heterogeneity within a single tumor is a common phenotype among various cancer types including squamous cell carcinoma. To further study the fundamentals and importance of heterogeneity of cell functions and its potential mechanisms, we performed single-cell RNA-seq (scRNA-seq) on human squamous cell carcinoma of the bladder (SCCB) and its corresponding physiologically normal epithelia. Extensive differentially expressed genes were uncovered by comparing cancer and normal single cells, which were preferentially enriched in cancer-correlated pathways, such as p53 signaling and bladder cancer pathway. Furthermore, the most diversely expressed genes were particularly enriched in MAPK signaling pathway, such as CACNG4, CACNA1E and CACNA1H, which involve in cancer evolution and heterogeneity formation. Co-expression network and hub-gene analyses revealed several remarkable "hub genes" of each regulatory module. Some of them are cancer related, such as POU2F3, NKD1 and CYP2C8, while LINC00189, GCC2 and OR9Q1 genes are rarely reported in human diseases. The genes within an interesting module are highly correlated with others, which could be treated as potential targets for SCCB patients. Our findings have fundamental implications for SCCB biology and therapeutic strategies.

Pubmed ID: 27602771 RIS Download

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NCBI Sequence Read Archive (SRA) (tool)

RRID:SCR_004891

Repository of raw sequencing data from next generation of sequencing platforms including including Roche 454 GS System, Illumina Genome Analyzer, Applied Biosystems SOLiD System, Helicos Heliscope, Complete Genomics, and Pacific Biosciences SMRT. In addition to raw sequence data, SRA now stores alignment information in form of read placements on reference sequence. Data submissions are welcome. Archive of high throughput sequencing data,part of international partnership of archives (INSDC) at NCBI, European Bioinformatics Institute and DNA Database of Japan. Data submitted to any of this three organizations are shared among them.

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Genome Reference Consortium (tool)

RRID:SCR_006553

Consortium that puts sequences into a chromosome context and provides the best possible reference assembly for human, mouse, and zebrafish via FTP. Tools to facilitate the curation of genome assemblies based on the sequence overlaps of long, high quality sequences.

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NOISeq (tool)

RRID:SCR_003002

Software used for the identification of differentially expressed genes from count data or previously normalized count data. It empirically models the noise distribution of count changes by contrasting fold-change differences (M) and absolute expression differences (D) for all the features in samples within the same condition. This reference distribution is then used to assess whether the M-D values computed between two conditions for a given gene is likely to be part of the noise or represent a true differential expression.

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