Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Language: Английский

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Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(8), P. 1243 - 1253

Published: Sept. 14, 2023

Language: Английский

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Technical challenges of studying early human development

Development, Journal Year: 2023, Volume and Issue: 150(11)

Published: June 1, 2023

ABSTRACT Recent years have seen exciting progress across human embryo research, including new methods for culturing embryos, transcriptional profiling of embryogenesis and gastrulation, mapping lineage trajectories, experimenting on stem cell-based models. These advances are beginning to define the dynamical principles development stages, tissues organs, enabling a better understanding before birth in health disease, potentially leading improved treatments infertility developmental disorders. However, there still significant roadblocks en route this goal. Here, we highlight technical challenges studying early propose ways means overcome some these constraints.

Language: Английский

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Why study human embryo development?

Developmental Biology, Journal Year: 2024, Volume and Issue: 509, P. 43 - 50

Published: Feb. 5, 2024

Understanding the processes and mechanisms underlying early human embryo development has become an increasingly active important area of research. It potential for insights into clinical issues such as pregnancy loss, origins congenital anomalies developmental adult disease, well fundamental biology. Improved culture systems preimplantation embryos, combined with new tools single cell genomics live imaging, are providing similarities differences between mouse development. However, access to material is still restricted extended embryos regulatory ethical concerns. Stem cell-derived models different phases can potentially overcome these limitations provide a scalable source explore postimplantation stages To date, clearly incomplete replicas normal but future technological improvements be envisaged. The environment studies remains fully resolved.

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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Historic obstacles and emerging opportunities in the field of developmental metabolism – lessons from Heidelberg

Development, Journal Year: 2024, Volume and Issue: 151(12)

Published: June 15, 2024

The field of developmental metabolism is experiencing a technological revolution that opening entirely new fields inquiry. Advances in metabolomics, small-molecule sensors, single-cell RNA sequencing and computational modeling present opportunities for exploring cell-specific tissue-specific metabolic networks, interorgan communication, gene-by-metabolite interactions time space. Together, these advances not only means by which biologists can tackle questions have challenged the centuries, but also young scientists with to define areas These emerging frontiers were at center highly interactive 2023 EMBO workshop 'Developmental metabolism: flows energy, matter, information'. Here, we summarize key discussions from this forum, emphasizing modern biology's challenges opportunities.

Language: Английский

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Integrated Molecular-Phenotypic Profiling Reveals Metabolic Control of Morphological Variation in Stembryos

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 5, 2023

SUMMARY Mammalian stem-cell-based models of embryo development (stembryos) hold great promise in basic and applied research. However, considerable phenotypic variation despite identical culture conditions limits their potential. The biological processes underlying this seemingly stochastic are poorly understood. Here, we investigate the roots by intersecting transcriptomic states morphological history individual stembryos across stages modeling post-implantation early organogenesis. Through machine learning integration time-resolved single-cell RNA-sequencing with imaging-based quantitative profiling, identify features predictive end-state. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias can be corrected metabolic interventions. Collectively, our work establishes divergent as drivers variation, offers broadly applicable framework to chart predict organoid systems. strategy leveraged control processes, ultimately increasing reproducibility vitro Highlights Time-resolved charting hundreds generates molecular fingerprints Machine identifies end-state Early cellular composition Metabolic interventions tune stembryo correct derailment differentiation outcomes

Language: Английский

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‘Ceci n’est pas un embryon?’ The ethics of human embryo model research

Nature Methods, Journal Year: 2023, Volume and Issue: 20(12), P. 1863 - 1867

Published: Dec. 1, 2023

Language: Английский

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Validation of a mouse 3D gastruloid-based embryotoxicity assay in reference to the ICH S5(R3) guideline chemical exposure list

Reproductive Toxicology, Journal Year: 2024, Volume and Issue: 125, P. 108558 - 108558

Published: Feb. 15, 2024

Language: Английский

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The logic of monsters: development and morphological diversity in stem-cell-based embryo models

Interface Focus, Journal Year: 2024, Volume and Issue: 14(5)

Published: Oct. 25, 2024

Organoids and stem-cell-based embryo models (SEMs) are imperfect organ or representations that explore a much larger space of possible forms, morphospace, compared to their

Language: Английский

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