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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2018 Feb 27

PMID 29478892

Citations 6

Authors

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

S Tamir Rashid

Affiliations

Soon will be listed here.

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.

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