Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

Vianello, Stefano; Lütolf, Matthias P.

doi:10.1016/j.devcel.2019.02.024

Cited by 71 publications

(78 citation statements)

References 147 publications

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“…The advent of in vitro models of mammalian development 8,9 provides several advantages: firstly, unlike embryos, such systems are amenable to systematic perturbations. The system size and its composition can be conveniently modulated by changing the type and the initial number of cells seeded.…”

Section: Introductionmentioning

confidence: 99%

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

Hashmi

Tlili

Perrin

et al. 2020

Preprint

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Shaping the animal body plan is a complex process that involves the spatial organization and patterning of different layers of cells. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned group of cells into structured territories is largely unknown. Here, using 3D aggregates of mouse embryonic stem cells, we study the formation of one of the three germ layers, the endoderm. We show that the endoderm can be generated from an epiblast-like state by a three-tier mechanism: a release of islands of E-cadherin expressing cells, their flow toward the tip of the 3D aggregate, and their segregation. In contrast to the prevailing view, this mechanism does not require epithelial to mesenchymal transitions and vice-versa but rather a fragmentation, which is mediated by Wnt/bcatenin, and a sorting process. Our data emphasize the role of signaling and cell flows in the establishment of the body plan.

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Section: Introductionmentioning

confidence: 99%

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

Hashmi

Tlili

Perrin

et al. 2020

Preprint

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“…In vitro 3D modelling of complex physiological behaviors is now becoming technological feasible for processses such as symmetry breaking, lumen formation, the patterning of cell differentiation and the formation of invasive tissue outgrowth (Vianello and Lutolf, 2019;Wan, 2016). However, the final shape of these large multicellular arrangements is the outcome of numerous processes that involve the regulations of intercellular interactions, cell shape and migration, the respective contributions of which are difficult to entangled.…”

Section: Introductionmentioning

confidence: 99%

Biophysical properties of intermediate states of EMT outperform both epithelial and mesenchymal states

Margaron

Nagai

Guyon

et al. 2019

Preprint

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Potential metastatic cells can dissociate from a primary breast tumor by undergoing an epithelial-to-mesenchymal transmission (EMT). Recent work has revealed that cells in intermediate states of EMT acquire an augmented capacity for tumor-cell dissemination. These states have been characterized by molecular markers, but the structural features and the cellular mechanisms that underlie the acquisition of their invasive properties are still unknown. Using human mammary epithelial cells, we generated cells in intermediate states of EMT through the induction of a single EMT-inducing transcription factor, ZEB1, and cells in a mesenchymal state by stimulation with TGFβ. In stereotypic and spatially-defined culture conditions, the architecture, internal organization and mechanical properties of cells in the epithelial, intermediate and mesenchymal state were measured and compared. We found that the lack of intercellular cohesiveness in epithelial and mesenchymal cells can be detected early by microtubule destabilization and the repositioning of the centrosome from the cell-cell junction to the cell center. Consistent with their high migration velocities, cells in intermediate states produced low contractile forces compared with epithelial and mesenchymal cells. The high contractile forces in mesenchymal cells powered a retrograde flow pushing the nucleus away from cell adhesion to the extracellular matrix. Therefore, cells in intermediate state had structural and mechanical properties that were distinct but not necessarily intermediate between epithelial and mesenchymal cells. Based on these observations, we found that a panel of triple-negative breast cancer lines had intermediate rather than mesenchymal characteristics suggesting that the structural and mechanical properties of the intermediate state are important for understanding tumor-cell dissemination.

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“…[ 67 ] The role of mechanical forces and geometry on embryonic development and possible uses of in vitro models of development to further decipher these factors have been well described elsewhere. [ 68 ] Although the aggregates cultured in this study are in free‐floating suspension culture within the microcavities, it would nevertheless be interesting to screen materials and coatings of different stiffness in the future and analyze the corresponding effect on aggregate morphogenesis. Future studies that enable confinement of the aggregates using microcavities of different geometrical shapes can yield further information regarding the role of mechanical confinement on aggregate elongation and axial specification.…”

Section: Figurementioning

confidence: 99%

A New Microengineered Platform for 4D Tracking of Single Cells in a Stem‐Cell‐Based In Vitro Morphogenesis Model

et al. 2020

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Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

Cited by 71 publications

References 147 publications

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids

Biophysical properties of intermediate states of EMT outperform both epithelial and mesenchymal states

A New Microengineered Platform for 4D Tracking of Single Cells in a Stem‐Cell‐Based In Vitro Morphogenesis Model

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