Studying evolution of the primary body axis in vivo and in vitro

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Aug. 31, 2021

The metazoan body plan is established during early embryogenesis via collective cell rearrangements and evolutionarily conserved gene networks, as part of a process commonly referred to gastrulation. While substantial progress has been achieved in terms characterizing the embryonic development several model organisms, underlying principles many patterning processes nevertheless remain enigmatic. Despite diversity (pre-)gastrulating embryo adult shapes across animal kingdom, axes, which are arguably most fundamental features, generally identical between phyla. Recently there renewed appreciation ex vivo vitro embryo-like systems events. Here, we briefly review key examples propose that similarities morphogenesis associated expression dynamics may reveal an developmental mode well provide further insights into role external or extraembryonic cues shaping embryo. In summary, argue can be employed inform previously uncharted aspects evolution rules.

Language: Английский

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Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids

Development, Journal Year: 2022, Volume and Issue: 149(20)

Published: Sept. 14, 2022

ABSTRACT The cellular microenvironment, together with intrinsic regulators, shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo appear benefit from hypoxic culture vitro. Yet, how influences transcriptional networks lineage choices remain poorly understood. Here, we investigated the molecular effects of acute prolonged on embryonic extra-embryonic cells as well functional impact potential. We find a temporal type-specific response including an primitive streak signature mediated by HIF1α. Using 3D gastruloid model, show that hypoxia-induced T expression enables symmetry breaking axial elongation absence exogenous WNT activation. When combined activation, enhances representation gastruloids, demonstrated highly enriched signatures gut endoderm, notochord, neuromesodermal progenitors somites. Our findings directly link microenvironment function provide rationale supportive applying physiological conditions models embryo development.

Language: Английский

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Carnegie in 4D? Stem-cell-based models of human embryo development

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 131, P. 44 - 57

Published: June 11, 2022

Language: Английский

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A gastruloid model of the interaction between embryonic and extra-embryonic cell types

Journal of Tissue Engineering, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 1, 2022

Stem-cell derived in vitro systems, such as organoids or embryoids, hold great potential for modeling vivo development. Full control over their initial composition, scalability, and easily measurable dynamics make those systems useful studying specific developmental processes isolation. Here we report the formation of gastruloids consisting mouse embryonic stem cells (mESCs) extraembryonic endoderm (XEN) cells. These XEN-enhanced (XEGs) exhibit neural epithelia, which are absent from mESCs only. By single-cell RNA-seq, imaging, differentiation experiments, demonstrate characteristics epithelial tissue. We further show that induce XEN to a visceral endoderm-like state. Finally, local inhibition WNT signaling production basement membrane by underlie neuroepithelial In summary, establish XEGs explore heterotypic cellular interactions consequences vitro.

Language: Английский

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Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112380 - 112380

Published: April 1, 2023

Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise spheroids self-organize into gastrulating containing cell types spatially functionally related extraembryonic compartments. Alternatively, cultured a droplet microfluidic device form elongated undergo axial organization reminiscent natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned neuronal paraxial mesoderm segmented somite-like structures. Transient suppression gradually increases DNA methylation genome wide repressive mark deposition at Nanog. Interestingly, cell-to-cell variations levels occur during early embryogenesis. Our approach provides proof principle potentially powerful strategies explore embryogenesis by targeting chromatin roadblocks fate change.

Language: Английский

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