Transcriptomic profiling of iPS cell derived hepatocyte-like cells reveals their close similarity to primary liver hepatocytes

Human induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) have been shown useful for the development of cell-based regenerative strategies and for modelling drug discovery. However, stem cell-derived HLCs are not identical in nature to primary human hepatocytes (PHHs), which could affect cell phenotype and, potentially model reliability. Therefore, we employed in-depth gene expression profiling of HLC and other important, relative cell types that identified clear similarities and differences between them at the transcriptional level. By gene set enrichment analysis, we identified genes critical for immune signaling pathways become downregulated upon HLC differentiation. Our analysis also found that TAV.HLCs exhibit a mild gene signature characteristic of acute lymphoblastic leukaemia but not other selected cancers. Importantly, HLCs present significant similarity to PHHs making them genuinely valuable for modelling human liver biology in vitro and for the development of prototype cell-based therapies for pre-clinical testing.
Keywords: liver, transcriptomic, stem cells, differentiation