Actuation Enhances Patterning in Human Neural Tube Organoids

Actuation Enhances Patterning in Human Neural Tube Organoids. Fattah, A. R. A., Daza, B., Rustandi, G., Berrocal-Rubio, M. A., Gorissen, B., Poovathingal, S., Davie, K., Cao, X., Rosenzweig, D. H., Lei, Y., Finnell, R., Verfaillie, C., Sampaolesi, M., Dedecker, P., Van Oosterwyck, H., Aerts, S., & Ranga, A. bioRxiv, Cold Spring Harbor Laboratory, 2020.

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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.Competing Interest StatementRF was CEO of Teratomic Consulting, LLC, which has been dissolved. He is also an associate editor of the journal Reproductive and Developmental Medicine, which provides his travel expenses.

@article {Fattah2020.09.22.308411,
	author = {Fattah, Abdel Rahman Abdel and Daza, Brian and Rustandi, Gregorius and Berrocal-Rubio, Miguel Angel and Gorissen, Benjamin and Poovathingal, Suresh and Davie, Kristofer and Cao, Xuanye and Rosenzweig, Derek Hadar and Lei, Yunping and Finnell, Richard and Verfaillie, Catherine and Sampaolesi, Maurilio and Dedecker, Peter and Van Oosterwyck, Hans and Aerts, Stein and Ranga, Adrian},
	title = {Actuation Enhances Patterning in Human Neural Tube Organoids},
	elocation-id = {2020.09.22.308411},
	year = {2020},
	doi = {10.1101/2020.09.22.308411},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {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.Competing Interest StatementRF was CEO of Teratomic Consulting, LLC, which has been dissolved. He is also an associate editor of the journal Reproductive and Developmental Medicine, which provides his travel expenses.},
	URL = {https://www.biorxiv.org/content/early/2020/09/22/2020.09.22.308411},
	eprint = {https://www.biorxiv.org/content/early/2020/09/22/2020.09.22.308411.full.pdf},
	journal = {bioRxiv}
}

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