King's College London

Research portal

Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications

Research output: Contribution to journalArticle

John Ong, Maria Paola Serra, Joe Segal, Ana-Maria Cujba, Soon Seng Ng, Richard Butler, Val Millar, Stephanie Hatch, Salman Zimri, Hiroyuki Koike, Karen Chan, Andrew Bonham, Michelle Walk, Ty Voss, Nigel Heaton, Ragai Mitry, Anil Dhawan, Daniel Ebner, Davide Danovi, Hiromitsu Nakauchi & 1 more S Tamir Rashid

Original languageEnglish
Pages (from-to)693-702
Number of pages10
JournalStem cell reports
Volume10
Issue number3
Early online date22 Feb 2018
DOIs
Publication statusPublished - 13 Mar 2018

Documents

King's Authors

Abstract

Use of hepatocytes derived from induced pluripotent stem cells (i-Heps) is limited by their functional differences in comparison with primary cells. Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization (high content analysis; HCA) of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm (Hepatocyte Likeness Index; HLI) for comparing the hepatic properties of cells against a physiological gold standard. The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC) lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin 411 as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454