Actuation enhances patterning in human neural tube organoids
| Autor: | Jorge Barrasa-Fano, Mar Cóndor, Peter Dedecker, Catherine M. Verfaillie, Hans Van Oosterwyck, Derek H. Rosenzweig, Miguel Angel Berrocal-Rubio, Stein Aerts, Richard H. Finnell, Xuanye Cao, Suresh Poovathingal, Maurilio Sampaolesi, Brian Daza, Gregorius Rustandi, Adrian Ranga, Abdel Rahman Abdel Fattah, Yunping Lei, Kristofer Davie, Benjamin Gorissen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pluripotent Stem Cells
DYNAMICS Neural Tube Computer science Science Cellular differentiation HYDROGELS Cell Culture Techniques Gene regulatory network General Physics and Astronomy Regenerative Medicine MOUSE Mechanotransduction Cellular Regenerative medicine Article General Biochemistry Genetics and Molecular Biology Cell Line Polyethylene Glycols Tissue engineering Single-cell analysis Ectoderm Organoid medicine Humans RNA-Seq CELL Induced pluripotent stem cell Biophysical methods Science & Technology Multidisciplinary Tissue Engineering SONIC HEDGEHOG Neural tube Cell Differentiation Hydrogels General Chemistry cell culture techniques cell differentiation cell line extracellular matrix humans hydrogels mechanotransduction cellular neural tube organoids pluripotent stem cells polyethylene glycols RNA-seq regenerative medicine single-cell analysis tissue engineering Extracellular Matrix NETWORKS Organoids Multidisciplinary Sciences medicine.anatomical_structure MORPHOGENESIS MECHANICS Science & Technology - Other Topics Single-Cell Analysis Biomedical engineering Neuroscience |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Mechanical forces, along with gene regulatory networks and cell-cell signalling, play an important role in the complex organization of tissues. Here the authors describe devices that actively apply mechanical force to developing neural tube, demonstrating that mechanical forces increase growth and enhance patterning. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink