Systems Level Approach Reveals the Correlation of Endoderm Differentiation of Mouse Embryonic Stem Cells with Specific Microstructural Cues of Fibrin Gels.

Antonio D'Amore, Joe Candiello, Antonio D'Amore, Satish Singh, Keith Task, Prashant Kumta, William R. Wagner, Ipsita Banerjee, Maria Jaramillo

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications.
    Original languageEnglish
    Number of pages9
    JournalJournal of the Royal Society Interface
    Volume11
    Publication statusPublished - 2014

    All Science Journal Classification (ASJC) codes

    • Biotechnology
    • Biophysics
    • Bioengineering
    • Biomaterials
    • Biochemistry
    • Biomedical Engineering

    Fingerprint

    Dive into the research topics of 'Systems Level Approach Reveals the Correlation of Endoderm Differentiation of Mouse Embryonic Stem Cells with Specific Microstructural Cues of Fibrin Gels.'. Together they form a unique fingerprint.

    Cite this