Date of Completion

7-25-2019

Embargo Period

7-30-2021

Keywords

Cherubism, RNA Sequencing, Bioinformatics (RNA Seq Data Analysis), Gene Expression Analysis, Skeletal Biology, Osteogenesis, Mesenchymal Stromal Cells, Hematopoietic Cells, Bone Biology

Major Advisor

Dr. Peter Maye

Associate Advisor

Dr. Ernst Reichenberger

Associate Advisor

Dr. Archana Sanjay

Associate Advisor

Dr. Blanka Rogina

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Cherubism is a rare autosomal dominant craniofacial disorder affecting pre-pubertal children. It is characterized by multilocular lesions in the mandible and/or maxilla consisting of numerous giant osteoclasts and extensive fibro-osseous tissue hyperplasia. Cherubism is caused due to gain-of-function missense mutations in Src Homology 3 Binding Protein 2 (SH3BP2), a gene encoding for a cytoplasmic adaptor protein. Like a classical adaptor protein, SH3BP2 assists in the relay of cellular signals and is responsible for appropriate cellular response to various environmental cues. Studies using a mouse model of cherubism carrying one of the most prevalent mutations in Sh3bp2have revealed systemic problems with inflammation and defects in osteogenesis. Given the limited mechanistic knowledge contributing to cherubism, the objective of my thesis was to investigate global changes in gene expression that occur in both the hematopoietic and mesenchymal cell populations present in a bone marrow culture model. Previous work has shown how bone marrow cultures derived from cherubism mice display impaired osteogenesis and spontaneous osteoclast formation. Through RNA sequencing, we have investigated changes in gene expression within the transcriptomic profiles of hematopoietic and mesenchymal cell populations that exist in these bone marrow cultures. Here, we present my findings from this investigation and speculate on the possible mechanisms of crosstalk that may exist between these two cell populations, which will potentially yield valuable insight into the molecular mechanisms behind cherubism and have broader implications for other inflammatory bone diseases.

Additional Files
RNA-Seq Specifications.docx (14 kB)
RNA-Seq Specifications
Hematopoietic Differential Gene Expression List with Normalized Counts (DESeq2 results).csv (613 kB)
Hematopoietic Differential Gene Expression List with Normalized Counts (DESeq2 results)
Mesenchymal Differential Gene Expression List with Normalized Counts (DESeq2 results).csv (459 kB)
Mesenchymal Differential Gene Expression List with Normalized Counts (DESeq2 results)
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