An epigenetic timer of gestation length in mice [scRNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1015200 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26028300_1.fastq.gz | Fastqsanger.gz | |||
| SRR26028300_2.fastq.gz | Fastqsanger.gz | |||
| SRR26028301_1.fastq.gz | Fastqsanger.gz | |||
| SRR26028301_2.fastq.gz | Fastqsanger.gz | |||
| SRR26028302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
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Project description:Timing mechanisms in biology remain poorly understood. As one prime example, little is known about the mechanisms that specify how long the gestating uterus will remain quiescent before entering labor1. Our lack of insight into this fundamental question, which applies to all mammalian species, also limits investigation into potential causes of preterm labor, a major human pregnancy complication. Here, we provide evidence that gestation length in mice is determined by an epigenetic timer that runs autonomously within the fibroblasts of the pregnant uterus. The timer is set during the peri-implantation period when select genomic loci establish appropriate levels of the repressive histone mark H3K27me3. These loci then progressively lose H3K27me3, thereby scheduling the uterine cell state transitions and associated gene expression changes of late gestation that are the proximal mediators of labor onset. Overwinding of the timer’s peri-implantation setpoint via genetic ablation of the histone demethylase KDM6B delays these transitions and extends gestation length. These results provide insight into how complex tissues employ epigenetic pathways to specify the timing of discrete biological events. We also anticipate that further dissection of the ways such uterine programming controls gestation length may suggest novel approaches for improving human pregnancy outcomes.
2024-12-20 | GSE242864 | GEO
Project description:An epigenetic timer of gestation length in mice [CUT&RUN]
| PRJNA1015689 | ENA
Project description:Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late gestation. By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K37me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy. Immediately after copulation, uterine fibroblasts engage in a locus-specific, epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3. This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation. This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor.
2025-01-06 | GSE242988 | GEO
Project description:The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian (‘Placental') mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.
2020-07-28 | GSE155170 | GEO
Project description:The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian (‘Placental') mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.
2020-08-26 | GSE155322 | GEO
Project description:Zygotic genome activation (ZGA) is a complex process which denotes the initiation of gene expression after fertilization. Deciphering the proper timing and genes involved in ZGA program is still a fundamental challenge in early embryo development. Here, we present a new ZGA gene identification framework, named ZGA-Timer, based on the timecourse pattern from RNA-seq data. By performing ZGA-Timer and siRNA technology, we confirmed Uqcc3 as a novel ZGA gene in mice. As a unique feature of ZGA-Timer, time-series RNA-seq data are modeled by a pattern recognition method and the onset of ZGA can be estimated in multiple species. ZGA-Timer outperforms current foldchange-based approaches. Furthermore, we investigate the epigenetic modifications and find that accessible chromatin predominately contributes to the regulation of ZGA genes. Moreover, ZGA genes show significant enrichment in housekeeping genes and cancer driver genes. Together, our ZGA-Timer framework provides a new approach to further understand the ZGA process.
2021-05-18 | GSE174530 | GEO
Project description:Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length
| PRJNA649314 | ENA
Project description:Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length
| PRJNA648914 | ENA
Project description:We grouped Foxp3+ cells from Foxp3 Timer reporter mice into Blue1, Blue2, Red1, and Red2, and sorted these cells according to their Timer fluorescence expression, and analysed the transcriptional profiles of those cells, comparing them with those of effector and naive T cells using RNA-seq. Foxp3 Timer reporter mice were sensitised by a hapten, and 5 days later, the draining LNs of the skin were analysed.
2018-07-10 | GSE89481 | GEO
Project description:Here, we performed single cell RNA sequencing (scRNA-seq) of human fetal kidney tissue samples from 2 individual biological specimens (13.7 and 15.4 weeks gestation). The data set is composed of approximately 10,000 cells from diverse renal lineages. Lineages captured include nephron progenitors, epithelium, stroma, immune, and endothelium.
2020-12-20 | E-MTAB-9083 | biostudies-arrayexpress