Epigenetic control of cell identities from epiblast to gastrulation

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Epigenetic modifications of chromatin are essential for the establishment cell identities during embryogenesis. Between embryonic days 3.5–7.5 murine development, major lineage decisions made that discriminate extraembryonic and tissues, primary germ layers formed, thereby laying down basic body plan. In this review, we cover contribution dynamic by DNA methylation, changes accessibility, histone modifications, in combination with transcription factors control gene expression programs different types. We highlight differences regulation enhancer promoter marks discuss their requirement specification. Importantly, many cases, lineage‐specific targeting epigenetic modifiers is carried out pioneer or master factors, sum mediate landscape cell‐type‐specific thus, identities.

Language: Английский

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Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos

Life Science Alliance, Journal Year: 2025, Volume and Issue: 8(4), P. e202402956 - e202402956

Published: Feb. 5, 2025

The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression, but the underlying mechanisms remain unclear. RNA-binding protein Trim71 is essential for development and serves as a potent regulator post-transcriptional expression. Here, we show that global deficiency induces severe defects mesoderm-derived cells at onset organogenesis. Murine -KO embryos displayed impaired primitive erythropoiesis, yolk sac vasculature, heart function, circulation, explaining embryonic lethality these mice. Tie2 Cre conditional knockout did not induce strong defects, showing expression endothelial their immediate progenitors dispensable survival. scRNA-seq E7.5 revealed transcriptomic arise already gastrulation, up-regulation mesodermal pioneer transcription factor Eomes. We identify Eomes direct target Trim71-mediated mRNA repression via NHL domain, demonstrating functional link between important regulatory genes. Taken together, our data suggest Trim71-dependent control establishes framework proper during

Language: Английский

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Post-transcriptional regulation in early cell fate commitment of germ layers

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 8, 2025

Cell differentiation during development is orchestrated by precisely coordinated gene expression programs. While some regulatory mechanisms are well understood, there a significant room to explore unresolved aspects of lineage choice and cell-fate decisions, as many events in these processes still not fully elucidated. Given that, influenced only transcriptional control but also post-transcriptional events. Here, we described the presence regulation on commitment across all three embryonic germ layers. We employed monolayer protocols map early human stem cell specification. This approach included obtaining representative populations from layers, followed sequencing both polysome-bound total RNAs. characterized our model its unique profile specific markers for each differentiation. RNA revealed consistent pattern upregulated downregulated when comparing transcriptome translatome By datasets, identified genes subjected layer differentiations categorized nature this regulation. GO analysis demonstrated that polysome profiling serves complementary technique, capturing nuances may be overlooked analyzing transcriptome. Finally, directly compared identify actively recruited translation machinery, uncovering features layer. Substantial modulation was found commitment, emphasizing potency nuanced These findings highlight regulation's critical role development, offering new insights into molecular

Language: Английский

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Identification of the core regulatory program driving NEUROD1-induced neuronal reprogramming

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115523 - 115523

Published: April 1, 2025

NEUROD1 (ND1)-induced astrocyte-to-neuron (AtN) conversion shows promise for treating neurological disorders. To gain insight into the molecular mechanisms of neuronal reprogramming, we established an in vitro system using primary cortical astrocyte cultures from postnatal rats and employed single-cell multiomics sequencing. Our findings indicate that initial primarily consisted immature astrocytes (ImAs), with potentially a minor presence radial glial cells. The ImAs initially went through intermediate state, activating both neural progenitor genes. Subsequently, they mimic vivo neurogenesis to acquire mature characteristics. We show ND1 acted as pioneer factor reshapes chromatin landscape neurons. This restructuring promotes expression neurogenic genes via inducing H3K27ac modification. Through integrative analysis various ND1-induced specification systems, identified 25 targets, including Hes6, key regulators. Thus, our work highlights role its downstream regulators reprogramming.

Language: Английский

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Developmental Toxicity and Skin Sensitization Potential of Synthetic Phenolic Antioxidants and Butylated Hydroxytoluene Transformation Products: Insights from Human Embryonic Stem Cell Models

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138300 - 138300

Published: April 1, 2025

Language: Английский

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A modular organization of mammalian gastrulation and the Spemann-Mangold organizer

Cells and Development, Journal Year: 2025, Volume and Issue: unknown, P. 204031 - 204031

Published: May 1, 2025

Language: Английский

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Eomesodermin in conjunction with the BAF complex promotes expansion and invasion of the trophectoderm lineage

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 31, 2025

Language: Английский

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