Single Cell RNA-seq Analysis of Telomeric Transcripts

Telomeres are repetitive DNA regions located at the termini of eukaryotic chromosomes. These structures prevent loss of functional genome at every cell division, as well as protect the chromosome ends from fusion with other chromosomes and from the inappropriate induction of DNA damage response. Factors critical to the function of telomeres include the Telomeric-Repeat Containing RNA (TERRA) transcribed from telomere regions. TERRA has been shown to exhibit cross-regulation with a number of telomere maintenance factors, including shelterin and telomerase. Additionally, TERRA is known to modulate telomeric chromatin as well as recruit a number of complexes to the telomeric DNA. Still, much of TERRA biology remains to be elucidated. In this study we sought to (1) identify and quantify TERRA expressions at the level of a single cell, (2) analyze gene-expression patterns associated with TERRA expression, and (3) investigate distinctions in cell phenotypes based on TERRA expression. To perform these analyses, we applied existing and newly developed tools on 25 tumor and normal publicly available single-cell RNA sequencing (scRNA-seq) datasets that profile the single-cell gene expressions of samples from prostate cancer, cholangiocarcinoma, neuroblastoma, normal fetal adrenal and normal embryo. Applying our novel method, for the first time we quantitatively detect TERRA expression at the single cell level, and show that TERRA-expressing cells exhibit whole-transcriptome profiles distinct from the rest of the cells in a dataset. This observation was consistent across different cancer and normal datasets. We show that evaluating TERRA expression at the dimension of a cell holds great potential for shedding light on TERRA biology.

Author

• Ulianova, Evgenia

Language

• en

Keyword

• TERRA
• telomere
• sequencing
• single-cell

Date created

• 2023

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Bioinformatics and Molecular Biochemistry

Degree

• M.S.

Advisor

• Horvath, Anelia

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/st74cr37t