Inferring the in vivo cellular program of developing bovine muscle from expression data
We outline an in vivo cellular program of bovine longissimus muscle development inferred from expression data from 60 days post conception to 3 months postnatal. Analytic challenges included changes in cellular composition, ambiguous ‘diagnostic’ markers of cell type and contrasts between cattle human and mouse myogenesis. Nevertheless, the expression profiles of the myosin isoforms support slow and fast muscle fibres emanating from primary and secondary myogenesis respectively, while expression of the prenatal myosin subunits is down regulated prior to birth. Of the canonical pro-myogenic Transcription Factors (TF), MYF6 and MYF5 are negatively co-expressed, with MYF6 displaying higher expression in the post-natal samples and MYF5, MYOG, HES6 and PAX7 displaying higher expression in early development. A set of TFs (SIX1, EYA2 and DACH2) considered important in undifferentiated murine cells were equally abundant in differentiated bovine cells. An examination of mammalian regulators of fibre composition, muscle mass and muscle metabolism, underscored the roles of PPARGC1A, TGF-ß signalling and the NHR4 Nuclear Hormone Receptors on bovine muscle development. Enriched among the most variably expressed genes from the entire data set were molecules regulating mitochondrial metabolism of carbohydrate (PDK4), fat (UCP3), protein (AGXT2L1) and high energy phosphate (CKMT2). The dramatic increase in the expression of these transcripts, which may enable the peri-natal transition to metabolic independence critical for new-born herbivores, provides surprising evidence for substantial developmental remodelling of muscle mitochondria and reflects changes in nutrient availability. Overall, despite differences in size, metabolism and physiology, the muscle structural subunit expression program appears very similar in ruminants, rodents and humans. Overall design: 2 treatment groups (Piedmontese by Hereford and Wagyu by Hereford cattle) across 10 LD muscle developmental time points, with 3 or 4 individuals per cell