Epigenetic regulation of early human embryo development

Cell stem cell, Год журнала: 2023, Номер 30(12), С. 1569 - 1584

Опубликована: Окт. 18, 2023

Studies of mammalian development have advanced our understanding the genetic, epigenetic, and cellular processes that orchestrate embryogenesis uncovered new insights into unique aspects human embryogenesis. Recent studies now produced first epigenetic maps early embryogenesis, stimulating ideas about reprogramming, cell fate control, potential mechanisms underpinning developmental plasticity in embryos. In this review, we discuss these regulation importance for safeguarding development. We also highlight unanswered questions key challenges remain to be addressed.

Язык: Английский

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Imprinting disorders

Nature Reviews Disease Primers, Год журнала: 2023, Номер 9(1)

Опубликована: Июнь 29, 2023

Язык: Английский

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Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest

Nature Cell Biology, Год журнала: 2024, Номер 26(2), С. 263 - 277

Опубликована: Янв. 18, 2024

Язык: Английский

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Environmental exposures influence multigenerational epigenetic transmission

Clinical Epigenetics, Год журнала: 2024, Номер 16(1)

Опубликована: Окт. 17, 2024

Epigenetic modifications control gene expression and are essential for turning genes on off to regulate maintain differentiated cell types. Epigenetics also modified by a multitude of environmental exposures, including diet pollutants, allowing an individual's environment influence resultant phenotypes clinical outcomes. These epigenetic due gene-environment interactions can be transmitted across generations, raising the possibility that influences occurred in one generation may beyond second generation, exerting long-lasting effect. In this review, we cover known mechanisms modification acquisition, reprogramming persistence, animal models human studies used understand multigenerational transmission, examples environmentally induced change its transmission generations. We highlight importance health not only current population but future generations will experience outcomes through inheritance.

Язык: Английский

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Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest

Developmental Cell, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Novel MEI1 mutations cause chromosomal and DNA methylation abnormalities leading to embryonic arrest and implantation failure

Molecular Genetics and Genomics, Год журнала: 2024, Номер 299(1)

Опубликована: Фев. 28, 2024

Язык: Английский

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Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis

Clinical Epigenetics, Год журнала: 2024, Номер 16(1)

Опубликована: Авг. 1, 2024

Abstract Background Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific patterns regulated through differential DNA methylation. A subgroup patients with imprinting have methylation changes at multiple loci, a condition referred to as multi-locus disturbance (MLID). MLID is recognised in most but not all and also found individuals atypical clinical features; the presence often alters management or prognosis affected person. Some cases caused by trans-acting genetic variants, frequently their mothers, counselling implications. There currently no consensus on definition MLID, indications prompting testing, molecular procedures methods for epigenetic diagnosis, recommendations laboratory reporting, considerations counselling, implications management. The purpose this study thus cover unmet need. Methods comprehensive literature search was conducted identification more than 100 articles formed basis discussions two working groups focusing diagnosis (n = 12 members) testing 19 members). Following eight months preparations regular online discussions, experts 11 countries compiled preliminary documentation determined questions be addressed during face-to-face meeting held attendance together four representatives patient advocacy organisations. Results In light available evidence expert consensus, we formulated 16 propositions 8 interim guidance MLID. Conclusions designation, phenotypes, propose alternative term syndrome. Due intrinsic variability guidelines underscore importance involving various fields ensure confident approach care. authors advocate global, collaborative efforts both basic translational research tackle numerous crucial that lack answers, suggest reconvening within next 3–5 years evaluate advancements update needed.

Язык: Английский

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Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans

Human Molecular Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Abstract Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions germline-derived DNA methylation that are maintained as differentially methylated (gDMRs) in somatic tissues. This form epigenetic regulation highly conserved mammals and thought to have co-evolved placentation. Tissue-specific gDMRs been identified human placenta, suggesting species-specific on unorthodox establishment or maintenance may be more widespread than previously anticipated. Non-canonical imprinting, reliant differential allelic H3K27me3 enrichment, has reported mouse rat pre-implantation embryos, overlapping long terminal repeat (LTR)-derived promoters. These non-canonical imprints lose parental allele-specific specificity, subsequently gaining same allele extra-embryonic tissues resulting placenta-specific, somatically acquired maternal DMRs. To determine if similar present we interrogated for a selected number loci, including (i) orthologues imprinted rat, (ii) promoters LTR-derived transcripts, (iii) CpG islands intermediate placenta-specific unmethylated gametes embryos. We failed identify any placenta whole villi samples. Furthermore, assayed were shown biallelically expressed indicating they not at earlier time points. Together, our work reiterates continued evolution mammals, which suggest linked differences during maternal-to-embryo transition integration retrotransposable elements.

Язык: Английский

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Gene expression changes in blastocyst hatching affect embryo implantation success in mice

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 6, 2025

In mammalian embryonic development, blastocyst hatching is essential for normal implantation and development of the fetus. We reported previously that blastocysts out zona pellucida (ZP) exhibited site preferences were associated with pregnancy outcomes. To characterize these differences, we analyzed transcriptomes in following developing mouse within 16 h hatching: expanding (E), from A-site (A), B-site (B), C-site (C), hatched (H), non-hatching (N). By principal component analysis hierarchical cluster analysis, determined gene expression profiles A B blastocysts, which resulted good fertility, clustered closely. C N poor closely, but distantly B. Embryos at B- vs. C-sites, pregnancy, showed 178 differentially expressed genes (DEGs), mainly involved immunity, correlated positively birth rate. These DEGs primarily regulated by transcription factors TCF24 DLX3. During hatching, immune-related regulated, such as Ptgs1, Lyz2, Il-α, Cfb (upregulated) Cd36 (downregulated). immunofluorescence staining, found C3 IL-1β on extra-luminal surface trophectoderm blastocyst, suggesting they play a role maternal-fetal interactions. As developed to fully state, 307 either upregulated factor ATOH8 or downregulated SPIC switch immune pathways. Based outcome, identified three patterns complex changes transcriptional regulation network failed successfully blastocysts. LASSO regression-based model using Cd36, Cfb, Cyp17a1 predict success. This study revealed diverse, multidimensional developmental fates during short-term indicated properties embryo had major effect suggest their preimplantation affect implantation. contributes our understanding

Язык: Английский

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Human-specific contributors to cleavage-stage embryonic arrest during maternal to zygotic transition

Developmental Cell, Год журнала: 2025, Номер 60(9), С. 1277 - 1279

Опубликована: Май 1, 2025

Язык: Английский

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