A 3D model of a human epiblast reveals BMP4-driven symmetry breaking

Šimunović, Mijo; Metzger, Jakob; Etoc, Fred; Yoney, Anna; Ruzo, Albert; Martyn, Iain; Croft, Gist F.; You, Dong Shin; Brivanlou, Ali H; Siggia, Eric D.

doi:10.1038/s41556-019-0349-7

Cited by 151 publications

(147 citation statements)

References 42 publications

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“…Unfortunately, formation of the ECM culture PASE embryoids is less reproducible than the micropattern embryoids at present, so these strategies need to be developed. Recently, the culture of dissociated hESCs in a mix of liquid hydrogel/ Matrigel has produced structures resembling day 10 epiblast (Simunovic et al, 2019) after 3 days; when cultured in intermediate concentrations of BMP4, these show breakage of antero-posterior symmetry and expression of markers of gastrulation. In light of these recent advances, we are starting to understand how cells self-organize and selfassemble, molecularly and cellularly, to generate discrete tissues and organs.…”

Section: Embryoidsmentioning

confidence: 99%

Adapting the 14-day rule for embryo research to encompass evolving technologies

Williams

Johnson

2020

Reproductive Biomedicine & Society Online

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We consider the scientific evidence that research on in-vitro development of embryos beyond 14 days is necessary. We then examine potential new developments in the use of stem cells to make embryoids or synthetic human entities with embryo-like features, and consider whether they also require legal control. Next, we consider the arguments advanced against extending the 14day period during which research on human embryos is currently permitted, and find none of them to be convincing. We end by proposing a new objective limit that could serve as a mechanism for regulating the use of embryos for research in vitro.

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Section: Embryoidsmentioning

confidence: 99%

Adapting the 14-day rule for embryo research to encompass evolving technologies

Williams

Johnson

2020

Reproductive Biomedicine & Society Online

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“…Therefore, efforts to understand human gastrulation have predominantly focused on in vitro models such as monolayers of human Embryonic Stem Cells (hESCs) cultured on circular micropatterns (Warmflash et al 2014). More recently, these have been extended to hESC colonies engrafted into chick embryos (Martyn et al 2018) or 3D cellular models derived from hESC (Simunovic et al 2019;Moris et al 2020). While these powerful approaches provide valuable insights, currently there is no in vivo data on the molecular control of human gastrulation to compare them against or further refine them.…”

Section: Introductionmentioning

confidence: 99%

A spatially resolved single cell atlas of human gastrulation

Mahammadov

Nakanoh

et al. 2020

Preprint

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Gastrulation is the fundamental process during the embryogenesis of all multicellular animals through which the basic body plan is first laid down. It is pivotal in generating cellular diversity coordinated with spatial patterning. Gastrulation in humans occurs in the third week following fertilization. Our understanding of this process in humans is extremely limited, and based almost entirely on experimental models. Here, we characterize in a spatially resolved manner the single cell transcriptional profile of an entire gastrulating human embryo approximately 16 to 19 days after fertilization. We used these data to provide the first unequivocal demonstration that human embryonic stem cells represent the early post implantation epiblast. We identified both primordial germ cells and red blood cells, which had never been characterized so early during human development. Comparison with mouse gastrula transcriptomes revealed many commonalities between the human and mouse but also several key differences, particularly in FGF signaling, that we validated experimentally. This unique dataset offers a unique glimpse into a central but generally inaccessible stage of our development, provides new context for interpreting experiments in other model systems and represents a valuable resource for guiding directed differentiation of human cells in vitro.

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“…The authors' model involves the generation of synthetic structures resembling the embryonic sac -which, later in development, becomes a fluid-filled bag and the embryo. It is a substantial advance on previous exciting models developed by this group 3 and others 4,5 because it reveals the spatial coordination of cell-differentiation events in the human embryo around the time of implantation. The events involved include the formation of the amniotic sac and a disc of cells inside it called the epiblast; the initial specification of primordial germ cells (PGCs; the eventual sperm or egg cells); and the start of a process called gastrulation.…”

Section: A M a N D E R T C L A R Kmentioning

confidence: 96%

Human embryo implantation modelled in microfluidic channels

Clark

2019

Nature

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A 3D model of a human epiblast reveals BMP4-driven symmetry breaking

Cited by 151 publications

References 42 publications

Adapting the 14-day rule for embryo research to encompass evolving technologies

Adapting the 14-day rule for embryo research to encompass evolving technologies

A spatially resolved single cell atlas of human gastrulation

Human embryo implantation modelled in microfluidic channels

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