Early human embryonic development: Blastocyst formation to gastrulation

Developmental Cell, Год журнала: 2022, Номер 57(2), С. 152 - 165

Опубликована: Янв. 1, 2022

Язык: Английский

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An ethical framework for human embryology with embryo models

Cell, Год журнала: 2023, Номер 186(17), С. 3548 - 3557

Опубликована: Авг. 1, 2023

A human embryo's legal definition and its entitlement to protection vary greatly worldwide. Recently, pluripotent stem cells have been used form in vitro models of early embryos that challenged definitions raised questions regarding their usage. In this light, we propose a refined an embryo, suggest "tipping points" for when embryo could eventually be afforded similar embryos, then revisit basic ethical principles might help draft roadmap the gradual, justified usage manner aims maximize benefits society.

Язык: Английский

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DNA methylation in mammalian development and disease

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Авг. 12, 2024

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding how this modification contributes development, ageing disease. In particular, the past decade seen many exciting mechanistic discoveries that have substantially expanded our appreciation for generic, evolutionarily ancient can be incorporated into robust epigenetic codes. Here, we summarize current distinct landscapes emerge over mammalian lifespan discuss they interact with other regulatory layers support diverse functions. We then review rising interest in alternative patterns found during senescence somatic transition cancer. Alongside advancements single-cell long-read sequencing technologies, collective insights made across these fields offer new opportunities connect biochemical genetic features cell physiology, developmental potential phenotype. Review, Smith et al. describe development within key disease states, as well different methyltransferases interface histone modifications proteins create maintain them.

Язык: Английский

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A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Май 7, 2021

Summary Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA-sequencing has been utilised unbiased transcriptional profiling. However, a well-organised integrated dataset, serving as universal reference benchmarking remains unavailable. Herein, we developed such reference, through integration six published datasets covering developmental stages from the zygote gastrula. Lineage annotations are contrasted validated with available non-human primate datasets. Using stabilised UMAP constructed web tool, where query can be projected annotated predicted cell identities. this examined several recent highlighting risk misannotation when relevant references lacking.

Язык: Английский

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Generating human blastoids modeling blastocyst-stage embryos and implantation

Nature Protocols, Год журнала: 2023, Номер 18(5), С. 1584 - 1620

Опубликована: Фев. 15, 2023

Язык: Английский

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A comprehensive human embryo reference tool using single-cell RNA-sequencing data

Nature Methods, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 14, 2024

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA sequencing has been utilized unbiased transcriptional profiling. However, an organized integrated RNA-sequencing dataset, serving as a universal reference benchmarking remains unavailable. Here we developed such through the integration six published datasets covering development from zygote gastrula. Lineage annotations are contrasted validated with available nonhuman primate datasets. Using stabilized Uniform Manifold Approximation Projection, constructed embryogenesis prediction tool, where query can be projected annotated predicted cell identities. this examined highlighting risk misannotation when relevant references not authentication.

Язык: Английский

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Highly efficient construction of monkey blastoid capsules from aged somatic cells

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 28, 2025

Abstract Blastoids—blastocyst-like structures created in vitro—emerge as a valuable model for early embryonic development research. Non-human primates stem cell-derived blastoids are an ethically viable alternative to human counterparts, yet the low formation efficiency of monkey blastoid cavities, typically below 30%, has limited their utility. Prior research predominantly utilized cells. In this work, we demonstrate efficient generation from induced pluripotent cells and somatic cell nuclear transfer derived aged monkeys, achieving 80% efficiency. We also introduce hydrogel-based microfluidics platform scalable reproducible production size-adjustable, biodegradable capsules, providing stable 3D structure mechanical protection. This advancement high-efficiency, capsules reprogrammed significantly enhances study holds promise regenerative medicine.

Язык: Английский

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Pluripotent cell states and fates in human embryo models

Development, Год журнала: 2025, Номер 152(7)

Опубликована: Апрель 1, 2025

ABSTRACT Pluripotency, the capacity to generate all cells of body, is a defining property transient population epiblast found in pre-, peri- and post-implantation mammalian embryos. As development progresses, undergo dynamic transitions pluripotency states, concurrent with specification extra-embryonic embryonic lineages. Recently, stem cell-based models pre- human have been developed using that capture key properties at different developmental stages. Here, we review early primate development, comparing states vivo cultured pluripotent representative these states. We consider how status starting influences embryo and, turn, what can learn about epiblast. Finally, discuss limitations questions arising from pioneering studies this emerging field.

Язык: Английский

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The primitive endoderm supports lineage plasticity to enable regulative development

Cell, Год журнала: 2024, Номер 187(15), С. 4010 - 4029.e16

Опубликована: Июнь 24, 2024

Mammalian blastocyst formation involves the specification of trophectoderm followed by differentiation inner cell mass into embryonic epiblast and extra-embryonic primitive endoderm (PrE). During this time, embryo maintains a window plasticity can redirect its cellular fate when challenged experimentally. In context, we found that PrE alone was sufficient to regenerate complete continue post-implantation development. We identify an in vitro population similar early vivo exhibits same potency form stem cell-based models, termed blastoids. Commitment is suppressed JAK/STAT signaling, collaborating with OCT4 sustained expression subset pluripotency-related transcription factors safeguard enhancer landscape permissive for multi-lineage differentiation. Our observations support notion factor persistence underlies regulative development highlight importance perturbed

Язык: Английский

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SyNPL: Synthetic Notch pluripotent cell lines to monitor and manipulate cell interactions in vitro and in vivo

Development, Год журнала: 2022, Номер 149(12)

Опубликована: Май 26, 2022

Cell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack efficient analysis tools. Here, we introduce SyNPL: clonal stem lines that employ optimised Synthetic Notch (SynNotch) technology to report cell-cell between engineered 'sender' 'receiver' cultured chimaeric mouse embryos. A modular design makes it straightforward adapt system for programming decisions non-cell-autonomously receiver response direct contact with sender cells. We demonstrate utility this enforcing neuronal at boundary two populations. In summary, provide new adaptation SynNotch could be used identify profile changes gene or protein expression result from defined populations culture embryos, can customised generate synthetic patterning fate decisions.

Язык: Английский

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