Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells

Abstract

Graphical abstract

Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue

“…Our results are consistent with similar studies comparing human primary hepatocytes to hPSC-HEP generated using an earlier generation of the differentiation protocol used in the present study (14) and with a different differentiation protocol analyzing several time points during the hepatic differentiation (39), where functional annotation analysis revealed that early stages of hepatic differentiation are GO enriched for terms in cell cycle and differentiation, while later stages are enriched for hepatocytes functional terms (14,39). This is in agreement with studies of in vivo liver tissues (6,24,28,29).…”

“…This is in agreement with studies of in vivo liver tissues (6,24,28,29). Furthermore, similar results of clusters of genes that are either not expressed or low in hPSC-HEP compared with primary hepa- tocytes are shown in (14), indicating remaining immature features of hPSC-HEP.…”

Highlight report: quality control of stem cell-derived hepatocytes

“…However, this optimistic point of view has also been critically discussed (Godoy et al 2013;Brulport et al 2007;Hengstler et al 2005). Upon the application of Omics technologies it has become possible to quantify the degree of differentiation based on an unbiased genome-wide expression analysis that can be performed by RNA-seq or gene array (Godoy et al 2015;Cameron et al 2015). The authors recommend an analysis pipeline that is applicable for all types of stem cell-derived cells (Godoy et al 2018).…”

Highlight report: acetaminophen hepatotoxicity

“…One of the most urgent clinical research fields seems to be the identification of biomarkers that predict more reliably whether a patient is in need of treatment Most likely the reason for resistance of cultivated hepatocytes to APAP is decreased expression CYP2E1 and further cytochrome P450 enzymes involved in APAP metabolic activation. It is well known that the isolation and cultivation stress lead to a rapid decrease in metabolizing enzymes in human hepatocytes (Godoy et al , 2015 and even more in rodents (Zellmer et al 2010;Heise et al 2012;Godoy et al 2009). Because of the relatively large discrepancy between APAP concentrations in vivo and higher concentrations chosen in many in vitro studies, it should be interpreted with caution, whether mechanisms observed in vitro at 10 mM and higher actually represent the in vivo situation.…”