Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A83]

Understanding the Role of the Extracellular Matrix on Cell Fate in Cortical Brain Organoids

Presenter: Gabriella Tamara Saint-Vil

Faculty Sponsor: ChangHui Pak

School: UMass Amherst

Research Area: Biochemistry and Molecular Biology

ABSTRACT

Human induced pluripotent stem cell (hiPSC)-derived 3D organoid models are a promising tool for gene and therapeutic target discovery, disease modeling, and developmental studies. Organoids are 3D self-organized tissues derived from stem cells that attempt to mimic an organ's key functions and biological processes. However, organoid models often lack an extracellular matrix (ECM), which provides crucial biochemical and biomechanical cues for tissue differentiation, homeostasis, and morphogenesis. A commonly used ECM for culturing neural organoids is Matrigel, which is derived from a mouse tumor. Tumor ECM differs from normal tissue ECM in its deposition, composition, and structural organization. Because the ECM plays a critical role in regulating biological processes, researching exogenous biocompatible ECM proteins for their ability to influence stem cell fate, growth, and differentiation is paramount for 3D organoid applications. 


To understand the various effects of an exogenous ECM varying in stiffness and composition on radial glial polarity, rosette quantity, and cellular differentiation, we are working with a hyaluron (HA) gel. Hyaluron is a glycosaminoglycan found in the ECM. The stiffness and ECM content of the gel can be modified, yielding different conditions. Immunohistochemistry is being conducted to quantify the expression and spatial distribution of phosphovimentin, phosphohistoneH3, and pericentrin, which are key markers of cellular behavior during division. Additionally, the spatial distribution of Sox2 and N-cadherin allows us to quantify rosettes under various conditions. Preliminary single-cell transcriptomics reveal expression of HA-interacting genes in our organoids, suggesting their capacity to interact with this gel.

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