Extracellular matrix microarrays to study inductive signaling for endoderm specification

Acta Biomaterialia
D F Braga MaltaG H Underhill

Abstract

During tissue development, stem and progenitor cells are faced with fate decisions coordinated by microenvironmental cues. Although insights have been gained from in vitro and in vivo studies, the role of the microenvironment remains poorly understood due to the inability to systematically explore combinations of stimuli at a large scale. To overcome such restrictions, we implemented an extracellular matrix (ECM) array platform that facilitates the study of 741 distinct combinations of 38 different ECM components in a systematic, unbiased and high-throughput manner. Using embryonic stem cells as a model system, we derived definitive endoderm progenitors and applied them to the array platform to study the influence of ECM, including the interactions of ECM with growth factor signaling, on the specification of definitive endoderm cells towards the liver and pancreas fates. We identified ECM combinations that influence endoderm fate decisions towards these lineages, and demonstrated the utility of this platform for studying ECM-mediated modifications to signal activation during liver specification. In particular, defined combinations of fibronectin and laminin isoforms, as well as combinations of distinct collagen subtypes, were s...Continue Reading

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Citations

Aug 16, 2016·Journal of Cell Communication and Signaling·Herman Yeger, Bernard Perbal
Oct 30, 2020·Frontiers in Bioengineering and Biotechnology·Raymond TranCorinne A Hoesli
Jan 9, 2021·APL Bioengineering·Katherine JoynerGregg A Duncan

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