ArticleActa biomaterialia2016
Extracellular matrix microarrays to study inductive signaling for endoderm specification.
Article in Acta biomaterialia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Integrated transcriptomic and proteomic analysis reveals isolation and culture associated molecular changes in neonatal porcine pancreatic cell clusters.Molecular biology reports · 2026Article
- Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications.Bioengineering & translational medicine · 2024Review
- Modulation of human iPSC-derived hepatocyte phenotype via extracellular matrix microarrays.Acta biomaterialia · 2022Article
- Elucidating Extracellular Matrix and Stiffness Control of Primary Human Hepatocyte Phenotype Via Cell Microarrays.Advanced materials interfaces · 2021Article
- High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology.Chemical reviews · 2021Review
- Observational
- Combinatorial ECM Arrays Identify Cooperative Roles for Matricellular Proteins in Enhancing the Generation of TH+ Neurons From Human Pluripotent Cells.Frontiers in cell and developmental biology · 2021Article
- Microrheology for biomaterial design.APL bioengineering · 2020Review
- Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors.Frontiers in bioengineering and biotechnology · 2020Review
- In Vitro Expansion of Keratinocytes on Human Dermal Fibroblast-Derived Matrix Retains Their Stem-Like Characteristics.Scientific reports · 2019Article
- Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer.Journal of visualized experiments : JoVE · 2019Article
- A High-throughput Cell Microarray Platform for Correlative Analysis of Cell Differentiation and Traction Forces.Journal of visualized experiments : JoVE · 2017Article
- CCN family of proteins: critical modulators of the tumor cell microenvironment.Journal of cell communication and signaling · 2016Article
- Organoids: fundamentals, present and future.Revista peruana de medicina experimental y salud publicaArticle
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Authors and funding
8 authors.
Funding
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 shown to influence SMAD pathway activation and the degree of hepatic differentiation. Overall, our systematic high-throughput approach suggests that ECM components of the microenvironment have modulatory effects on endoderm differentiation, including effects on lineage fate choice and cell adhesion and survival during the differentiation process. This platform represents a robust tool for analyzing effects of ECM composition towards the continued improvement of stem cell differentiation protocols and further elucidation of tissue development processes. STATEMENT OF SIGNIFICANCE: Cellular microarrays can provide the capability to perform high-throughput investigations into the role of microenvironmental signals in a variety of cell functions. This study demonstrates the utility of a high-throughput cellular microarray approach for analyzing the effects of extracellular matrix (ECM) in liver and pancreas differentiation of endoderm progenitor cells. Despite an appreciation that ECM is likely involved in these processes, the influence of ECM, particularly combinations of matrix proteins, had not been systematically explored. In addition to the identification of relevant ECM compositions, this study illustrates the capability of the cellular microarray platform to be integrated with a diverse range of cell fate measurements, which could be broadly applied towards the investigation of cell fate regulation in other tissue development and disease contexts.
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