Dynamic and distinct histone modifications facilitate human trophoblast lineage specification
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1016306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26049449_1.fastq.gz | Fastqsanger.gz | |||
| SRR26049449_2.fastq.gz | Fastqsanger.gz | |||
| SRR26049450_1.fastq.gz | Fastqsanger.gz | |||
| SRR26049450_2.fastq.gz | Fastqsanger.gz | |||
| SRR26049451.fastq.gz | Fastqsanger.gz |
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Project description:The placenta serves as an essential organ for nurturing fetal growth throughout pregnancy. Histone modification is a crucial regulatory mechanism involved in numerous biological processes and development. Nevertheless, there remains a significant gap in our understanding regarding the precise mechanisms and extent to which various histone modifications influence the critical process of trophoblast lineage differentiation, which is fundamental to placental development. Here, we conducted a comprehensive mapping of H3K4me3, H3K27me3, H3K9me3, and H3K27ac loci during trophoblast stem cells (TSC) differentiation into syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT) to investigate the regulatory roles and dynamic changes in histone modifications in trophoblast lineage specification.
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Project description:We characterized the trophoblast stem cell epigenome and gene expression profiles in rat and mouse. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast stem cells derived from rat and mouse. Furthermore, for mouse, we profiled key trophoblast stem cell factors Elf5, Cdx2, and Eomes. We found that enhancer regions (defined as distal regions of H3K27ac/H3K4me1 enrichment) were enriched for species-specific endogenous retroviral elements.
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Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast giant cells derived from mouse. Furthermore, we profiled digital expression profiles (3' RNA-Seq) for in vivo trophoblast giant cells samples from e9.5 wildtype mouse trophoblast giant cells. We found that underrepresented domains in trophoblast giant cells are enriched for repressive marks and anti-correlate with active marks and transcription.
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Project description:The arising of trophectoderm (TE) is a hallmark event in preimplantation development during embryogenesis. However, little is known about the mechanisms underlying TE specification. Our findings demonstrate that depletion of Rif1 breaks down the barriers to conversion of trophoblast stem cells (TSCs). Rif1-null induced TSCs show typical TE properties, and differentiation potentials to terminal trophoblast lineages. Global transcriptome analysis reveals that Rif1-null activates 2-cell embryo (2C) related genes and induces a totipotent-like state, which is probably the main reason for the conversion of TSCs from Rif1-null embryonic stem cells (ESCs). Chimeric assays further confirm that Rif1-null ESCs can contribute to TE, further yielding TSCs in vitro. Over-expression of a downstream gene of Rif1, Hmgn3, can also activate 2C related genes and facilitate induction of TSCs. Here, we report two pioneer genes regulating conversion of TSCs and provide insights for investigating the mechanisms of TE specification.
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Project description:To address early human placenta development, we aimed to characterize the cell surface proteomic profile of early trophoblast cells in an effort to understand trophoblast heterogeneity and population dynamics. We quantify cell surface protein expression in early first trimester human placentas using a high throughput flow cytometry screen of 370 Cluster of Differentiation (CD) antigens and confidently identified 23 increasing and 13 decreasing markers of dynamic populations between weeks 6 and 10 of human placenta development. We were particularly interested in transient trophoblast populations expressing either EpCAM (CD326) or CDCP1 (CD318) populations of trophoblasts. Immunohistochemistry analysis revealed these CD antigens are expressed by discrete cells with EpCAM localized to trophoblast in the proximal villi columns while CDCP1 is expressed by cells in the distal columns. Multi-color flow analysis confirmed independence of CDCP1 and EPCAM expressing cell populations and identified EpCAM cells as positive for EGFR. Microarray analysis of gene expression indicated EpCAM+/EGFR+ and EGFR+ cells showed high degree of gene expression similarities to villus cytotrophbolast but that loss of EpCAM expression was concomitant with exit from the cell cycle as EpCAM/EGFR cell were mitotically active while CDCP1 positive trophoblast are enriched in gene sets related to immune regulation functions and cell cycle/cell division and have significant similar gene expression to extravillous cytotrophoblast. Our study indicates at least two distinct subpopulations of cytotrophoblasts exit in the early first trimester and that the column likely maintains pools of actively dividing progenitor cells giving rise to the developing placenta villus tree.
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