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Leveraging complex interactions between signaling pathways involved in liver development to robustly improve the maturity and yield of pluripotent stem cell-derived hepatocytes

Raggi, C.; M'Callum, M.-A.; Pham, Q. T.; Gaub, P.; Selleri, S.; Baratang, N.; Mangahas, C. L.; Cagnone, G.; Reversade, B.; Joyal, J.-S.; Paganelli, M.

2020-09-03 developmental biology
10.1101/2020.09.02.280172 bioRxiv
Show abstract

Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLC) have shown great potential as an alternative to primary human hepatocytes (PHH) for in vitro modeling. Several differentiation protocols have been described to direct PSC towards the hepatic fate, although the resulting HLC have shown more a fetal than adult phenotype. Here, by leveraging recent knowledge of the signaling pathways involved in liver development, we describe a robust, scalable protocol that allows to consistently generate high-quality HLC from both ESC and iPSC. Such HLC are comparable to adult PHH in terms of key mature liver functions and proved suitable to assess drug hepatotoxicity, as a proof of concept of their potential as a physiologically representative alternative for in vitro modeling.

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The top 7 journals account for 50% of the predicted probability mass.

1
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.