Meeting Abstract
Tendon size can vary widely among closely related taxa, e.g. mice vs. jerboas, suggesting that the tendons of these species may experience different growth regimes. In mice, the period from birth to roughly 1 month of age is characterized by extensive tendon growth. Conventional wisdom states that this growth is driven by expansion of the extracellular matrix with negligible cell proliferation. However, our previous work has shown that tendon cells remain proliferative through postnatal day (P) 14, after matrix production has already begun to increase. Thus, this period is a time of dynamic change within the tendon, but the molecular mechanisms governing these transitions are largely unknown. We performed RNA sequencing on mouse tendons sampled weekly from P0 to P35 to identify transcriptomic signatures associated with the changing cell proliferation dynamics. Approximately 22% of detected genes were found to be differentially expressed (DE) at some point during the time series (adj. p < 0.01). To gain a more detailed understanding of temporal gene expression patterns during this period, we subset all DE genes by fitting observed counts to different models of expression over time. Gene Ontology and Gene Set Enrichment Analyses of these subsets suggest that biological processes involved in cell proliferation and differentiation dominate the earlier time points, while cell communication and cytoskeleton organization become more important later. The midpoint of this time series exhibits upregulation of genes involved in the secretion and binding of extracellular matrix, but downregulation of molecules that control cell adhesion. These results suggest that postnatal tendon growth involves three stages: the proliferative phase, matrix secretory phase, and organization phase.
