Elbakri, Rania
(2024)
Whole blood transcriptome profiling in juvenile systemic sclerosis patients reveals active immune upregulation and enhanced fibrotic signature.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Juvenile Systemic Sclerosis (jSSc) is a rare chronic autoimmune disorder with understudied pathogenesis, characterized by skin thickness and multisystem organ involvement, associated with high morbidity. The University of Pittsburgh Medical Centers (UPMC) Children’s Hospital of Pittsburgh hosts a Pediatric Scleroderma Center (Torok Director) allowing the collection of blood for the biorepository paired with clinical phenotypic data to start to identify the factors associated with disease in jSSc.
RNA sequencing was performed on peripheral blood samples of jSSc (n=22) with age/sex matched healthy controls (n=17) using Illumina NovaSeq6000. Data was analyzed in Partek software and DESeq2. Differentially expressed genes (DEGs) were defined based on with a significance cut off (false discovery rate 0.05) and fold change of ≤1.5 or ≥ 1.5. Principal component and t-distributed stochastic neighbor embedding analyses were used to cluster samples based on gene expression profiles. Further analysis was conducted to determine pathway enrichment and dysregulated pathways
DEseq2 analysis identified 263 DEGs comparing jSSc with HC. Upregulated genes included several protein coding genes which play roles in collagen, extracellular matrix (ECM) formation, and adaptive immune responses. All findings have important roles in connective tissue disorder. Gene enrichment analysis showed activation in inflammatory, adaptive immune response pathways in jSSc.
As a result, jSSc transcriptional profile provides valuable insights into the gene expressions patterns in immune cells. It demonstrated upregulation of genes highlighting their roles in the pathogenesis of jSSc involving fibrosis formation, vasculopathy, and dysregulation of immune cells
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
1 July 2024 |
| Date Type: |
Publication |
| Defense Date: |
28 June 2024 |
| Approval Date: |
1 July 2024 |
| Submission Date: |
1 July 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
60 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
RNA sequencing
Juvenile Systemic Sclerosis
autoimmune disorder
peripheral blood |
| Date Deposited: |
01 Jul 2024 20:05 |
| Last Modified: |
01 Jul 2024 20:05 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46640 |
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