Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(7), P. 1058 - 1071.e5

Published: May 31, 2024

The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in blastocyst. Research with human embryos challenging. Thus, stem models that reproduce differentiation provide valuable alternatives. We show here naive pluripotent (PSC) to proceeds via reversion a transitional ICM-like state from which emerges concordance trajectory blastocysts. identified window when fibroblast growth factor (FGF) signaling critical for specification. Revisiting FGF revealed inhibition early blastocyst suppresses formation. In vitro, induction of synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports establishes conservation lineage specification between mice humans. Overall, this study demonstrates utility PSC-based elucidating mechanistic features embryogenesis.

Language: Английский

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

Nature Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

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Pluripotent cell states and fates in human embryo models

Development, Journal Year: 2025, Volume and Issue: 152(7)

Published: April 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.

Language: Английский

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Three‐dimensional stem cell models of mammalian gastrulation

BioEssays, Journal Year: 2024, Volume and Issue: 46(12)

Published: Aug. 28, 2024

Abstract Gastrulation is a key milestone in the development of an organism. It period cell proliferation and coordinated cellular rearrangement, that creates outline body plan. Our current understanding mammalian gastrulation has been improved by embryo culture, but there are still many open questions difficult to address because intrauterine embryos low number specimens. In case humans, additional difficulties associated with technical ethical challenges. Over last few years, pluripotent stem models being developed have potential become useful tools understand gastrulation. Here we review these special emphasis on gastruloids provide survey methods produce them robustly, their uses, relationship embryos, prospects as well limitations.

Language: Английский

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Criteria for the standardization of stem-cell-based embryo models

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1625 - 1628

Published: Sept. 2, 2024

Language: Английский

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Species Choice and Model Use: Reviving Research on Human Development

Journal of the History of Biology, Journal Year: 2024, Volume and Issue: 57(2), P. 231 - 279

Published: June 1, 2024

Abstract While model organisms have had many historians, this article places studies of humans, and particularly our development, in the politics species choice. Human embryos, investigated directly rather than via animal surrogates, gone through cycles attention neglect. In past 60 years they moved from sidelines to center stage. Research was resuscitated anatomy, launched reproductive biomedicine, molecular genetics, stem-cell science, made attractive developmental biology. I explain surge interest terms rivalry with models reliance on them. The greater involvement medicine human reproduction, especially vitro fertilization, gave access fresh sources material that fed critiques extrapolation mice met demands for clinical relevance or “translation.” Yet much revival depended models. Supply infrastructures digital standards, including biobanks virtual atlases, emulated community resources organisms. Novel culture, imaging, molecular, postgenomic methods were perfected less precious samples. Toing froing mouse affirmed necessity exemplary mammal its insufficiency justified inquiries into humans. Another kind model—organoids embryo-like structures derived stem cells—enabled experiments encouraged organization a new field, humans has competed counted

Language: Английский

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Methodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2624 - 2624

Published: March 14, 2025

Animal embryos are vital tools in scientific research, providing insights into biological processes and disease mechanisms. This paper explores their historical contemporary significance, highlighting the shift towards refinement of vitro systems as alternatives to animal experimentation. We have conducted a data review relevant literature on use research synthesized highlight importance this model for progress ethical considerations regulations surrounding embryo emphasizing minimizing suffering while promoting through principles replacement, reduction, refinement. Embryos from wide range species, including mammals, fish, birds, amphibians, reptiles, play crucial experimental role enabling us understand factors such substance toxicity, embryonic development, metabolic pathways, physiological processes, etc., that contribute advancement sciences. To apply effectively, it is essential match objectives with most appropriate methodology, ensuring chosen approach scope study.

Language: Английский

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Stem cell-based models of early human development

Development, Journal Year: 2025, Volume and Issue: 152(8)

Published: April 15, 2025

ABSTRACT Stem cell-based embryo models (SCBEMs) are structures generated from three-dimensional (3D) culture of pluripotent stem cells and their derivatives, utilizing mechanical and/or chemical cues to facilitate lineage differentiation, self-organization morphogenesis. These partially mimic early embryos, which would otherwise be difficult access. SCBEMs have been established in mice, livestock, nonhuman primates humans. Here, we focus on recently developed human models, with an emphasis the peri-implantation stage aspects development these recapitulate.

Language: Английский

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Bioengineering embryo models

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Language: Английский

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Recent Advances in 3D Cultures

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4189 - 4189

Published: April 10, 2024

Methods and protocols for creating complex 3D cell culture systems have been rapidly advancing in the past decade from perspective of biomaterials [...].

Language: Английский

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