Journal
GIGASCIENCE
Volume 4, Issue -, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1186/s13742-015-0091-4
Keywords
Single-cell transcriptome; HeLa; HPV; Virus; Tumor heterogeneity; Cancer; RNA splicing
Categories
Funding
- National Basic Research Program of China [2011CB809203]
- Chinese 863 Program [2012AA02A201, 2012AA02A502]
- Guangdong Innovative Research Team Program [2009010016]
- Guangdong Enterprise Key Laboratory of Human Disease Genomics
- Shenzhen Municipal Government of China [CXB201108250094A, CXB201108250096A]
- Science, Technology and Innovation Committee of Shenzhen Municipality [JSGG20140702161347218]
- National Natural Science Fund [81272899, 81172510]
- Discipline booster plan of Xi Jing Hospital [XJZT12Z07]
- Shanxi Fund [2013K12-03-03]
- Xi'an Fund [SF1323(3)]
- Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
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Background: Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas. Recent single-cell RNA-seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied. HeLa is a well characterized HPV+ cervical cancer cell line. Result: We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip. Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing. Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions. Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level. By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins. Conclusion: Our results reveal the heterogeneity of a virus-infected cell line. It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers.
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