Poster 16
Presenter: Kwangbom Choi
Thursday, 4:00 – 6:00pm
Kwangbom Choi, Cheryl L. Ackert-Bicknell, Gary A. Churchill, Matthew A. Hibbs The Jackson Laboratory, Trinity University
Osteoblasts are mononuclear cells that differentiate from mesenchymal stem cells (MSCs). They are responsible for the formation and the mineralization of the osteoid matrix to produce healthy bone tissue. Understanding the genetic and molecular bases of normal osteoblast development is a key for developing new anabolic treatments for osteoporosis.
To investigate the maturation process of osteoblasts, we generated a time course RNA-seq dataset at nine equally-spaced time points from purified murine MSC samples. The primary cell cultures were derived from 5 diverse genetic backgrounds so we can characterize the differences and commonalities across the different strains. We also measured the mineralization levels of these cultures, as well as in vivo histomorphometric data at each time point in order to coordinate the timings of the transcriptional events among the 5 examined strains.
We targeted our analysis efforts to the transcriptional dynamics, for example, temporal variation of isoform-specificity or allele-specificity, associated with the phenotypic changes we measured. For this purpose, we developed a new Expectation-Maximization (EM) algorithm to estimate isoform-specific and allele-specific expression abundance from F1 mice. Through the application of our new approach followed by the differential co-expression analysis, we identified core transcriptional responses conserved across multiple strains, as well as unique expression events possibly relevant to the phenotypic variation among the particular genetic backgrounds. We believe that our systems biology perspective on the new level of transcriptional details offered by RNA-seq analysis contributed to a better understanding of the osteoblastogenesis.