Biology subjects

Fattah, A. R. A.

Publications and source records attributed to Fattah, A. R. A..

2 recordsLinked to original sources

bioRxiv2022

Extracellular matrix flow guides in-vitro epithelial morphogenesis

Changes in spatial localization of the extracellular matrix (ECM) are necessary for establishing morphogenesis in multiple developmental contexts. Both ECM motion and tissue deformation require multicellular scale coordination, however the interplay between them remain largely unexplored. Here, we reveal a novel mechanism coupling morphogenetic events and epithelia-driven ECM flow in vitro. We show that exposure to ECM components triggers periodic morphogenesis of dome-shaped structures in human pluripotent stem cell (hPSC) monolayers, driven by directional ECM flow. We show that this flow is initiated by local symmetry breaking events, is driven by microvilli and requires unperturbed flow conditions, microvilli function, and cytoskeletal contractility. An in silico model shows that a reaction-diffusion-like mechanism is responsible for organizing local morphogenesis into global tissue-wide events. We validate this model by predicting changes in cell patterning landscape during mesoderm differentiation, and demonstrate changes in cellular identity by immunohistochemistry and scRNAseq. These results demonstrate that transport of ECM over epithelia, termed ECM flow, is a major contributor in sustaining morphogenesis and differentiation. Our in vitro approach suggests that ECM flow may be a broadly conserved mechanism guiding multi-cellular morphogenesis and may be further explored to investigate the role of ECM transport in other model systems.

bioengineering↗

bioRxiv2020

Actuation Enhances Patterning in Human Neural Tube Organoids

Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.

bioengineering↗