Three‐dimensional stem cell models of mammalian gastrulation

Turner, David A.; Martinez Arias, Alfonso

doi:10.1002/bies.202400123

Cited by 4 publications

References 130 publications

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Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos

Ying,

Nichols

2024

BioEssays

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Pluripotent stem cell lines derived from preimplantation mouse embryos have opened opportunities for the study of early mammalian development and generation of genetically uncompromised material for differentiation into specific cell types. Murine embryonic stem cells are highly versatile and can be engineered and introduced into host embryos, transferred to recipient females, and gestated to investigate gene function at multiple levels as well as developmental mechanisms, including lineage segregation and cell competition. In this review, we summarize the biomedical motivation driving the incremental modification to culture regimes and analyses that have advanced stem cell research to its current state. Ongoing investigation into divergent mechanisms of early developmental processes adopted by other species, such as agriculturally beneficial mammals and birds, will continue to enrich knowledge and inform strategies for future in vitro models.

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Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos

Ying,

Nichols

2024

BioEssays

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The logic of monsters: development and morphological diversity in stem-cell-based embryo models

Cao,

Garai,

DiFrisco

et al. 2024

Interface Focus.

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Organoids and stem-cell-based embryo models (SEMs) are imperfect organ or embryo representations that explore a much larger space of possible forms, or morphospace, compared to their in vivo counterparts. Here, we discuss SEM biology in light of seminal work by Pere Alberch, a leading figure in early evo-devo, interpreting SEMs as developmental ‘monstrosities’ in the Alberchian sense. Alberch suggested that ordered patterns in aberrant development—i.e. ‘the logic of monsters’—reveal developmental constraints on possible morphologies. In the same vein, we detail how SEMs have begun to shed light on structural features of normal development, such as developmental variability, the relative importance of internal versus external constraints, boundary conditions and design principles governing robustness and canalization. We argue that SEMs represent a powerful experimental tool to explore and expand developmental morphospace and propose that the ‘monstrosity’ of SEMs can be leveraged to uncover the ‘hidden’ rules and developmental constraints that robustly shape and pattern the embryo.

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Programming the elongation of mammalian cell aggregates with synthetic gene circuits

Courte,

Chung,

Jain

et al. 2024

Preprint

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A key goal of synthetic morphogenesis is the identification and implementation of methods to control morphogenesis. One line of research is the use of synthetic genetic circuits guiding the self-organization of cell ensembles. This approach has led to several recent successes, including control of cellular rearrangements in 3D via control of cell-cell adhesion by user-designed artificial genetic circuits. However, the methods employed to reach such achievements can still be optimized along three lines: identification of circuits happens by hand, 3D structures are spherical, and effectors are limited to cell-cell adhesion. Here we show the identification, in a computational framework, of genetic circuits for volumetric axial elongation via control of proliferation, tissue fluidity, and cell-cell signaling. We then seek to implement this design in mammalian cell aggregatesin vitro.We start by identifying effectors to control tissue growth and fluidityin vitro. We then combine these new modules to construct complete circuits that control cell behaviors of interest in space and time, resulting in measurable tissue deformation along an axis that depends on the engineered signaling modules. Finally, we contextualizein vitroandin silicoimplementations within a unified morphospace to suggest further elaboration of this initial family of circuits towards more robust programmed axial elongation. These results and integratedin vitro/in silicopipeline demonstrate a promising method for designing, screening, and implementing synthetic genetic circuits of morphogenesis, opening the way to the programming of various user-defined tissue shapes.

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Three‐dimensional stem cell models of mammalian gastrulation

Cited by 4 publications

References 130 publications

Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos

Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos

The logic of monsters: development and morphological diversity in stem-cell-based embryo models

Programming the elongation of mammalian cell aggregates with synthetic gene circuits

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