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Dissertation/Thesis Abstract

X-Chromosome Inactivation in Human Adipose-Derived Mesenchymal Stem Cells Using Single Cell RNA Sequencing
by Ibeawuchi, Helen, M.S., The George Washington University, 2020, 69; 28000134
Abstract (Summary)

Mesenchymal stem cells are multipotent stem cells that have the ability to differentiate into different cell types including adipocytes. Adipose derived mesenchymal stem cells (ADSCs) are considered to be the best source for mesenchymal cell isolation since adipose tissue is easily accessible and can be obtained using less invasive procedures. These cells have promising clinical applications in medicine. During embryonic development, X-inactivation occurs randomly in individual cells. ADSCs just like other cells undergo X-inactivation. X-chromosome inactivation (XCI) is a phenomenon in which one X chromosome in the female is randomly silenced. Some genes; however, escape this process and some of the escapee genes have been linked to genetic diseases.

The main goal of this study was to develop and assess an approach to estimate cell-type specific XCI from single cell RNA-sequencing (scRNA-seq) data generated using 3’protocol and utilizing Unique Molecular Identifiers (UMIs). To this end, the specific objectives of this study were to identify the different cell types present in adipose-derived mesenchymal stem cells, establish their XCI status, and compare the findings to existing knowledge in relation to disease and medicine, using single cell RNA sequencing (scRNA-seq) data. To perform this research, we used publicly available scRNA-seq data from 26,640 human adipose-derived mesenchymal stem cells from three healthy females. First, we estimated the different cells types. Across the three individuals, we identified adipose cells, erythrocytes, neutrophils, and naïve B-cells. Within each cell type, we then assessed the expressed variant allele fraction (VAFRNA) at all heterozygous Single Nucleotide Variant (SNV) positions on the X-chromosome. We identified cell-type specific genes that escape the chromosome X-inactivation. These included some genes not previously described as escapees in other tissues. The relationship between these escapee genes and their association with certain diseases was also established. Our future plan is to study the molecular mechanisms and biological pathways related to XCI escapees in health and disease. This will help in the understanding of the clinical implications and possibly suggests management strategies of these diseases to provide a better clinical outcome.

Indexing (document details)
Advisor: Horvath, Anelia
Commitee: Shook, Brett
School: The George Washington University
Department: Biochemistry & Systems Biology
School Location: United States -- District of Columbia
Source: MAI 81/12(E), Masters Abstracts International
Subjects: Bioinformatics, Medicine, Health sciences
Keywords: Escapee genes, Random monoallelic Expression, Single cell RNA sequencing, Single nucleotide variant, Variant allele fraction, X-chromosome inactivation
Publication Number: 28000134
ISBN: 9798641002811
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