Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures

Sözen, Berna; Amadei, Gianluca; Cox, Andy; Wang, Ran; Na, Ellen; Czukiewska, Sylwia; Chappell, Lia; Voet, Thierry; Michel, Geert; Jing, Naihe; Glover, David M.; Zernicka‐Goetz, Magdalena

doi:10.1038/s41556-018-0147-7

Cited by 262 publications

(277 citation statements)

References 38 publications

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“…Nevertheless, recent advances have seen the generation of synthetic gastrulating embryos in vitro from multiple embryonic and extra-embryonic cell types (Harrison, Sozen, Christodoulou, Kyprianou, & Zernicka-Goetz, 2017;Sozen et al, 2018). Using omics-based approaches on mouse embryos may be challenging due to the requirement of ample tissue samples for ChIP-seq and proteomics analysis.…”

Section: Bu Ild Ing the G Ene Reg Ul Atory Ne T Work (G Rn) Of He Amentioning

confidence: 99%

Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

et al. 2019

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Development of an embryo is driven by a series of molecular instructions that control the differentiation of tissue precursor cells and shape the tissues into major body parts. LIM homeobox 1 (LHX1) is a transcription factor that plays a major role in the development of the embryonic head of the mouse. Loss of LHX1 function disrupts the morphogenetic movement of head tissue precursors and impacts on the function of molecular factors in modulating the activity of the WNT signaling pathway. LHX1 acts with a transcription factor complex to regulate the transcription of target genes in multiple phases of development and in a range of embryonic tissues of the mouse and Xenopus. Determining the interacting factors and transcriptional targets of LHX1 will be key to unraveling the ensemble of factors involved in head development and building a head gene regulatory network. K E Y W O R D S gene regulatory network, head development, Lhx1, mouse, Xenopus

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Section: Bu Ild Ing the G Ene Reg Ul Atory Ne T Work (G Rn) Of He Amentioning

confidence: 99%

Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

et al. 2019

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“…This self-organization occurs in response to BMP and Wnt signaling active during the cavity fusion process (58,59). Finally, the markers of primordial germ cells become expressed in a spatialtemporal manner characteristic of development.…”

Section: Self-organization Of Embryonic and Extraembryonic Stem Cellsmentioning

confidence: 99%

“…The migration of ESCs to form the mesoderm layer, sandwiched between ESC-derived epiblast and XEN-derived visceral endoderm, and replacement of the XEN-layer with definitive endoderm are the hallmarks of early-to-mid gastrulation (59). This points to the essential requirement for the correct choreography of cells from embryonic and the two extraembryonic tissues to achieve correct form.…”

Section: Self-organization Of Embryonic and Extraembryonic Stem Cellsmentioning

confidence: 99%

“…This event has been observed after substituting the ECM with the third stem cell type, extraembryonic endoderm (XEN) stem cells (Fig. 1), which provide the natural basement membrane (59,60). As a result, the formed structures look markedly similar to early postimplantation embryos in morphology, gene expression, and signaling communication.…”

Section: Self-organization Of Embryonic and Extraembryonic Stem Cellsmentioning

confidence: 99%

“…They break symmetry at the embryonic and extraembryonic boundary with the induction of AP patterning and EMT, leading to mesoderm and definitive endoderm formation (59). This self-organization occurs in response to BMP and Wnt signaling active during the cavity fusion process (58,59).…”

Section: Self-organization Of Embryonic and Extraembryonic Stem Cellsmentioning

confidence: 99%

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357 Occupational exposure to selenium compounds, its effect on biological parameters and markers of diabetes

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Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size and inaccessibility of the embryo. The generation of stem cell models of the embryo represents a powerful system with which to dissect this complexity. Control of geometry, modulation of the physical environment, and priming with chemical signals reveal the intrinsic capacity of embryonic stem cells to make patterns. Adding the stem cells for the extraembryonic lineages generates three-dimensional models that are more autonomous from the environment and recapitulate many features of the pre-and postimplantation mouse embryo, including gastrulation. Here, we review the principles of self-organization and how they set cells in motion to create an embryo.

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Single‐Step Biofabrication of In Situ Spheroid‐Forming Compartmentalized Hydrogel for Clinical‐Sized Cartilage Tissue Formation

van Loo,

Schot,

Gurian

et al. 2023

Adv Healthcare Materials

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Abstract3D cellular spheroids offer more biomimetic microenvironments than conventional 2D cell culture technologies, which has proven value for many tissue engineering applications. Despite the beneficiary effects of 3D cell culture, clinical translation of spheroid tissue engineering is challenged by the limited scalability of current methods of spheroid formation. Although the recent adoption of droplet microfluidics can provide a continuous production process, the use of oils and surfactants, the generally low throughput, and requirement of additional biofabrication steps hinder clinical translation of spheroid culture. Here we report on the use of clean (e.g., oil‐free and surfactant‐free), ultra‐high throughput (e.g., 8.5 ml/min, 10.000 spheroids/s), single‐step, in‐air microfluidic biofabrication of spheroid forming compartmentalized hydrogels. We demonstrated that this novel technique could reliably produce 1D, 2D, and 3D compartmentalized hydrogel constructs in the form of fibers, plane, and volumes, which each allowed for distinct (an)isotropic orientation of hollow spheroids forming compartments. The spheroids that were produced within ink‐jet bioprinted compartmentalized hydrogels outperformed 2D cell cultures in terms of chondrogenic behavior. Moreover, we demonstrated that the cellular spheroids could be harvested from compartmentalized hydrogels and used to build shape‐stable centimeter‐sized biomaterial‐free living tissues in a bottom‐up manner. Consequently, it is anticipated that in‐air microfluidic production of spheroid forming compartmentalized hydrogels could advance the production and use of cellular spheroids for various biomedical applications.This article is protected by copyright. All rights reserved

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Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures

Cited by 262 publications

References 38 publications

Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

357 Occupational exposure to selenium compounds, its effect on biological parameters and markers of diabetes

Single‐Step Biofabrication of In Situ Spheroid‐Forming Compartmentalized Hydrogel for Clinical‐Sized Cartilage Tissue Formation

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