Construction of a Mammalian Embryo from Embryonic Stem Cells Instructed by Morphogen Gradients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA596522 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10735722.fastq.gz | Fastqsanger.gz | |||
| SRR10735723.fastq.gz | Fastqsanger.gz | |||
| SRR10735724.fastq.gz | Fastqsanger.gz | |||
| SRR10735725.fastq.gz | Fastqsanger.gz | |||
| SRR10735726.fastq.gz | Fastqsanger.gz |
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Project description:Generating properly organized and differentiated embryonic structures in vitro from aggregates of pluripotent cells remains a major challenge. In a living embryo, the interplay in between signaling molecules known as morphogens and their antagonists lead to gradients of activity that instruct cells about their fate, leading to patterning and morphogenesis. Here we show that experimentally engineering a morphogen signaling center within an aggregate of mouse pluripotent stem cells is sufficient to mimic the function of an embryo organizer and to trigger embryonic development. The resulting embryoids are remarkably well patterned along anterior-posterior and dorsal-ventral axes, generate three germ layers through a process of gastrulation and differentiate germ layer derivatives (including notochord, vasculature, neural tube, neural crest, endoderm) similar to an authentic embryo at E9-E9.5.
2021-04-25 | GSE142309 | GEO
Project description:Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates of mouse embryonic stem cells with an experimentally engineered morphogen signalling centre, that functions as an organizer, results in the development of embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses show that these embryoids form the three germ layers through a gastrulation process and that they exhibit a wide range of developmental structures, highly similar to neurula-stage mouse embryos. Embryoids are organized around an axial chordamesoderm, with a dorsal neural plate that displays histological properties similar to the murine embryo neuroepithelium and that folds into a neural tube patterned antero-posteriorly from the posterior midbrain to the tip of the tail. Lateral to the chordamesoderm, embryoids display somitic and intermediate mesoderm, with beating cardiac tissue anteriorly and formation of a vasculature network. Ventrally, embryoids differentiate a primitive gut tube, which is patterned both antero-posteriorly and dorso-ventrally. Altogether, embryoids provide an in vitro model of mammalian embryo that displays extensive development of germ layer derivatives and that promises to be a powerful tool for in vitro studies and disease modelling.
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Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
2019-09-15 | GSE133526 | GEO
Project description:During development, morphogens build tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been unfeasible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised Sonic Hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenously-expressed SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor Myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.
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Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
2024-11-15 | GSE254439 | GEO
Project description:Purpose: Construction of 3D zebrafish spatial transcriptomics data for studying the establishment of AP axis. Methods: We performed serial bulk RNA-seq data of zebrafish embryo at three development points. Using the published spatial transcriptomics data as references, we implemented Palette to infer spatial gene expression from bulk RNA-seq data and constructed 3D embryonic spatial transcriptomics. The constructed 3D transcriptomics data was then projected on zebrafish embryo images with 3D coordinates, establishing a spatial gene expression atlas named Danio rerio Asymmetrical Maps (DreAM). Results: DreAM provides a powerful platform for visualizing gene expression patterns on zebrafish morphology and investigating spatial cell-cell interactions. Conclusions: Our work used DreAM to explore the establishment of anteroposterior (AP) axis, and identified multiple morphogen gradients that played essential roles in determining cell AP positions. Finally, we difined a hox score, and comprehensively demonstrated the spatial collinearity of Hox genes at single-cell resolution during development.
2024-04-08 | GSE262578 | GEO
Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Project description:Purpose: Characterization of cell types in wild-type and TCTN2 KO human neural tube organoids (hNTOs). Methods: Wild-type and TCTN2 KO hNTOs were harvested at day11. Libraries were prepared using Single Cell 3′Library & gel Bead kit v3.1 (10x Genomics, Cat# PN-1000121) according to the manufacturer’s protocol for 10000 cells recovery. Results: 13 neural progenitor cells were detected in wild-type hNTOs, and TCTN2 deficiency led to reduction of ventral progenitors cells. Conclusions: A well-organized nueral tube organoid was constructed by applying BMP and SHH morphogen gradients.
2024-02-06 | GSE254817 | GEO
Project description:Some aspects of pattern formation in developing embryos can be described by nonlinear reaction-diffusion equations. An important class of these models accounts for diffusion and degradation of a locally produced single chemical species. At long times, solutions of such models approach a steady state in which the concentration decays with distance from the source of production. We present analytical results that characterize the dynamics of this process and are in quantitative agreement with numerical solutions of the underlying nonlinear equations. The derived results provide an explicit connection between the parameters of the problem and the time needed to reach a steady state value at a given position. Our approach can be used for the quantitative analysis of tissue patterning by morphogen gradients, a subject of active research in biophysics and developmental biology.
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Project description:morphogen-signalling modifying factors in Panarthropoda
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