Back to Search
Start Over
Single-cell imaging reveals unexpected heterogeneity of telomerase reverse transcriptase expression across human cancer cell lines
- Source :
- Proceedings of the National Academy of Sciences. 116:18488-18497
- Publication Year :
- 2019
- Publisher :
- Proceedings of the National Academy of Sciences, 2019.
-
Abstract
- Telomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) is usually the limiting component for telomerase activation, numerous studies have measured TERT mRNA levels in populations of cells or in tissues. In comparison, little is known about TERT expression at the single-cell and single-molecule level. To address this, we analyzed TERT expression across 10 human cancer lines using single-molecule RNA fluorescent in situ hybridization (FISH) and made several unexpected findings. First, there was substantial cell-to-cell variation in number of transcription sites and ratio of transcription sites to gene copies. Second, previous classification of lines as having monoallelic or biallelic TERT expression was found to be inadequate for capturing the TERT gene expression patterns. Finally, spliced TERT mRNA had primarily nuclear localization in cancer cells and induced pluripotent stem cells (iPSCs), in stark contrast to the expectation that spliced mRNA should be predominantly cytoplasmic. These data reveal unappreciated heterogeneity, complexity, and unconventionality in TERT expression across human cancer cells.
- Subjects :
- Cytoplasm
Telomerase
RNA Splicing
Biology
Gene Expression Regulation, Enzymologic
Transcription (biology)
Cell Line, Tumor
Neoplasms
Humans
Telomerase reverse transcriptase
RNA, Messenger
Promoter Regions, Genetic
Induced pluripotent stem cell
Gene
Alleles
In Situ Hybridization, Fluorescence
Cell Nucleus
Multidisciplinary
RNA
Telomere
Biological Sciences
Molecular biology
Gene Expression Regulation, Neoplastic
HEK293 Cells
Cancer cell
Single-Cell Analysis
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....921e1428e7780e62308e07f1fd237203