Defining lncRNAs Associated with CHO Cell Growth and IgG Productivity by RNA-Seq I

Small-scale bioreactors used in Chinese hamster ovary (CHO) cell line development allow transcriptomic studies on multiple cell lines. Here we define the CHO cell long non-coding RNA (lncRNA) transcriptome from cells grown in controlled miniature bioreactors under fed-batch conditions using RNA-Seq to identify lncRNAs and how the expression of these changes throughout growth and between IgG producers. We identify lncRNAs associated with productivity and growth characteristics, finding that Adapt15, linked to ER stress, GAS5, linked to mTOR signalling/growth arrest, and PVT1, linked to Myc expression, are differentially regulated during fed-batch culture and whose expression relates to productivity and growth. Changes in (non)-coding RNA expression between the seed train and the equivalent day of fed-batch culture are also reported, showing large differences in gene expression between these, and compared with existing datasets. Collectively, we present a comprehensive lncRNA CHO cell profiling and identify targets for engineering growth and productivity characteristics of CHO cells. Overall design: Coding and lncRNAs by RNA-Seq in CHO cells at differente time points obtained through Illumina ribosomal RNA-depleted RNA-Seq