培養肉プロセス最適化のための付着性および懸濁性ニワトリ線維芽細胞株の比較トランスクリプトーム解析

For the cultivated meat industry, food-relevant cell lines with optimal attributes for industrial bioprocesses are needed. One key trait is suspension-proficiency, or the ability of cells to proliferate in non-adherent culture conditions, to achieve high viable cell densities and streamline cell harvests. The limited success with suspension adaptations of animal cells for cultivated meat restricts the number of non-adherent cell lines suitable for cost-efficient biomass production. Here, we investigated transcriptional profiles of chicken embryonic fibroblasts (DF-1 s) as they progressed from adherent to suspension culture using time-series RNA sequencing. From this analysis, we identified that DF-1s adapt to their non-adherent conditions by suppressing non-essential metabolism and tightly regulating cell junctions in response to oxidative stress and cell detachment. Based on these findings, we propose a putative novel mechanism enabling suspension proficiency in DF-1 s, where mitogen-activated protein kinase (MAPK) p38δ sequesters TEA domain (TEAD) proteins to the cytoplasm and promotes Yes-associated protein (YAP) binding to Forkhead box protein 1 (FoxO1), simultaneously causing cell-matrix dissociation and antioxidant production. The outcome of this work is a deeper understanding of mechanisms that drive the generation of suspension cell lines, with a goal to translate these findings to other food-relevant cell lines and develop expanded cell options for the field.