Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 497 - 512.e23

Published: Jan. 18, 2023

Language: Английский

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Growth anisotropy of the extracellular matrix shapes a developing organ

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 3, 2023

Abstract Final organ size and shape result from volume expansion by growth changes contractility. Complex morphologies can also arise differences in rate between tissues. We address here how differential guides the morphogenesis of growing Drosophila wing imaginal disc. report that 3D morphology results elastic deformation due to anisotropy epithelial cell layer its enveloping extracellular matrix (ECM). While tissue grows plane, bottom ECM occurs is reduced magnitude, thereby causing geometric frustration bending. The elasticity, are fully captured a mechanical bilayer model. Moreover, expression Matrix metalloproteinase MMP2 controls envelope. This study shows controllable constraint whose intrinsic directs developing organ.

Language: Английский

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Controlling human organoid symmetry breaking reveals signaling gradients drive segmentation clock waves

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 513 - 527.e19

Published: Jan. 18, 2023

Language: Английский

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Multimodal characterization of murine gastruloid development

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(6), P. 867 - 884.e11

Published: May 19, 2023

Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development compare them with the in vivo embryo. We developed high-throughput handling imaging pipeline to spatially monitor symmetry breaking report an early spatial variability pluripotency determining binary response Wnt activation. Although gastruloid-core revert pluripotency, peripheral become primitive streak-like. These two populations subsequently break radial initiate axial elongation. By performing compound screen, perturbing thousands gastruloids, derive phenotypic landscape infer networks genetic interactions. Finally, using dual modulation, improve formation anterior existing model. This work provides understand how gastruloids develop generate complex patterns vitro.

Language: Английский

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Collective intelligence: A unifying concept for integrating biology across scales and substrates

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 28, 2024

Abstract A defining feature of biology is the use a multiscale architecture, ranging from molecular networks to cells, tissues, organs, whole bodies, and swarms. Crucially however, not only nested structurally, but also functionally: each level able solve problems in distinct problem spaces, such as physiological, morphological, behavioral state space. Percolating adaptive functionality one competent subunits higher functional organization requires collective dynamics: multiple components must work together achieve specific outcomes. Here we overview number biological examples at different scales which highlight ability cellular material make decisions that implement cooperation toward homeodynamic endpoints, intelligence by solving cell, tissue, whole-organism levels. We explore hypothesis province groups animals, an important symmetry exists between science swarms competencies cells other systems scales. then briefly outline implications this approach, possible impact tools field diverse for regenerative medicine synthetic bioengineering.

Language: Английский

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Cellular and molecular control of vertebrate somitogenesis

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 517 - 533

Published: Feb. 28, 2024

Language: Английский

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Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Language: Английский

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Stem-cell-based embryo models for fundamental research and translation

Nature Materials, Journal Year: 2020, Volume and Issue: 20(2), P. 132 - 144

Published: Nov. 16, 2020

Language: Английский

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Mouse gastrulation: Coordination of tissue patterning, specification and diversification of cell fate

Mechanisms of Development, Journal Year: 2020, Volume and Issue: 163, P. 103617 - 103617

Published: May 27, 2020

Language: Английский

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Viscoelasticity and Adhesion Signaling in Biomaterials Control Human Pluripotent Stem Cell Morphogenesis in 3D Culture

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(43)

Published: Sept. 9, 2021

Abstract Organoids are lumen‐containing multicellular structures that recapitulate key features of the organs, and increasingly used in models disease, drug testing, regenerative medicine. Recent work has 3D culture to form organoids from human induced pluripotent stem cells (hiPSCs) reconstituted basement membrane (rBM) matrices. However, rBM matrices offer little control over microenvironment. More generally, role matrix viscoelasticity directing lumen formation remains unknown. Here, viscoelastic alginate hydrogels with independently tunable stress relaxation (viscoelasticity), stiffness, arginine–glycine–aspartate (RGD) ligand density study hiPSC morphogenesis culture. A phase diagram shows how these properties is reported. Higher RGD fast promote viability, proliferation, apicobasal polarization, formation, while slow at low densities triggers apoptosis. Notably, hiPSCs maintain pluripotency for much longer times than reported Lumen regulated by actomyosin contractility accompanied translocation Yes‐associated protein (YAP) nucleus cytoplasm. The results reveal as a potent factor regulating cell provide new insights into engineered biomaterials may be leveraged build organoids.

Language: Английский

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