Omics comparisons of HEK293 cell lines empha-size patterns of similar clonal divergence of de-rived progeny cell lines and highlight key changes upon adherent to suspension growth adaptation

The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production and is today used for manufacturing of several therapeutic pro-teins and viral vectors. Despite this increasing popularity there is still limited knowledge of the detailed genetic and composition of derivatives of this strain. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.