Investigating Global Changes in Gene Expression in a Murine Model of Cherubism

Purpose: To identify the mechanistic changes that lead to impaired osteogenesis and spontaneous osteoclast formation in both the hematopoietic and mesenchymal cell populations the makeup bone marrow cultures derived from cherubism mice (Sh3bp2KI/KI). Methods: Bone marrow cultures derived from wild type and cherubism mice were grown for seven days. On day seven, hematopoietic and mesenchymal cell types were sorted using CD45 and Sca1 cell surface markers. CD45+Sca1+ identified the hematopoietic population. CD45-Sca1+ identified the mesenchymal population. Total RNA was prepared from cell sorted populations. RNA quality was confirmed, ribosomal RNAs were depleted, libraries were prepared, and paired-end sequencing was performed on a illumina platform. We performed this study using six biological replicates. Results: Gene expression differences were identified Conclusions: Our study, for the first time, identifies the impact of a cherubism mutation on the global transcriptome of hematopoietic and mesenchymal cells extracted from murine bone marrow stromal cultures. With this study, we have found novel molecular signatures that are consistent with the cherubism phenotype (inflammation, bone loss, and fibrosis). Overall design: mRNA profile of cherubism hematopoietic and mesenchymal cells extracted from day 7 murine bone marrow stromal cultures