Exploring metaboloepigenetic variability in bovine fibroblast lines

Somatic cell-based reproductive technologies (SCRTs) offer a promising approach for preserving the genetic diversity of threatened species. SCRTs require the nuclear reprogramming of a donor somatic cell, which has low success rates (1%-5%) and can vary significantly between individuals and cell lines derived from the same individual. Somatic and pluripotent cells differ in several key characteristics, and donor cells presenting more pluripotent-like traits have been found to result in improved reprogramming outcomes. Here, we characterized 18 standardized fibroblast cell lines from six Angus bulls for several of these characteristics at the inter- and intra-individual levels: bioenergetic status, targeted metabolite abundance, global DNA methylation levels, and presence of key histone modifications. Differences in the metaboloepigenetic profiles of these cell lines were observed at both inter- and intra-individual levels. By integrating these data, we positioned cell lines along a somatic-to-pluripotent-like continuum and identified a reduced set of features that captured the dominant separation between profiles. Although functional reprogramming outcomes were not assessed here, these results provide a data-driven framework to prioritise donor cell lines for prospective induced pluripotent stem cell/somatic cell nuclear transfer validation and to guide the development of practical biomarker panels for SCRT workflows.