Mitochondrial Sequencing and Single-Cell RNA Sequencing Combination

Thursday, September 7, 2023

2:00 PM-4:00 PM

BIOMED Master's Thesis Defense

Title:
Mitochondrial Sequencing and Single-Cell RNA Sequencing Combination: A Promising Technique To Effectively Understand the Cell Dynamics in Breast Cancer

Speaker:
Anh Nguyen, Master's Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
 
Advisor:
Katherine Nathanson, MD
Pearl Basser Professor
Deputy Director Abramson Cancer Center
Department of Translational Medicine and Human Genetics
Perelman School of Medicine
University of Pennsylvania

Details:
As demand for new and effective treatments for cancer increases, insight into cell dynamics in cancers is necessary. In 2018, a new technique called single-cell RNA sequencing (scRNA-seq) was developed, opening a new door to understanding individual cell fates and gene expressions in complex organisms. However, the technique alone still has limitations on the scale and accuracy when it comes to tracking somatic nuclear mutations.

To address this issue, I propose combining mitochondrial DNA sequencing (mtDNA-seq) with scRNA-seq with the hypothesis that the combination will enhance the accuracy of lineage tracing in humans and resolve the clonal population; somatic mtDNA mutations will serve as "natural barcodes" to accurately indicate cellular relationships. Breast tissues, both tumor and normal, were collected from cancer patients and prophylactic patients. The tissues were then processed through tissue dissociation to obtain single cells and then through 10X protocol to gain cDNA. The resulting cDNAs were processed for both scRNA-seq and mtDNA-seq.

The findings indicate that 1) different tissue dissociation methods can result in different tissue profile in scRNA-seq analysis, 2) cells from different cell types develop from a common progenitor, and 3) cancerous cells develop from polyclonal mutations. This combined technique is reliable enough to generate a comprehensive “cell map” that allows a deeper understanding of the heterogeneity and dynamics in cancers, with the potential to discover new screening targets and better treatments.

Contact Information

Natalia Broz
njb33@drexel.edu