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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266196 | GEO | 2025/01/08

REPOSITORIES: GEO

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

Project description:The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs) and hundreds of placental-specific imprinted domains. Furthermore, the placental ‘methylome’ has been the focus of extensive study for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional epigenetic studies; however, whether the hTSC epigenome recapitulates primary cytotrophoblast, remains poorly described. In this study, we demonstrate that hTSCs exhibit an atypical methylome, with DNA methylation present over transcribed gene bodies but a complete loss of placental PMDs. Using single-cell RNA-seq from human embryogenesis, hTSCs display a notable absence of DNMT3L expression. Ectopic expression of DNMT3L in hTSCs restored placental PMDs. DNMT3L-expressing hTSCs showed comparable stemness but failed to syncytialise in organoid culture, associated with hypermethylation of STB transcription factor motifs. These findings reveal that DNMT3L is essential in establishing the human placental methylome and that DNMT3L downregulation is necessary for successful trophoblast differentiation.

2025-01-08 | GSE266194 | GEO

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

| PRJNA1106286 | ENA

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

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Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-30 | GSE139058 | GEO

Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids.

Project description:Zika virus (ZIKV) infection during pregnancy threatens pregnancy and fetal health. However, the infectivity and pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using human trophoblast stem cells (hTSCs), we demonstrated that hTSCs were permissive to ZIKV infection, and resistance to ZIKV increased with hTSC differentiation. Combining gene knockout and transcriptome analysis, we demonstrated that the intrinsic expression of AXL and TIM-1, and the absence of potent interferon (IFN)-stimulated genes (ISGs) and IFNs contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived trophoblast organoid (hTSC-organoid), we demonstrated that ZIKV infection disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further demonstrated that ZIKV infection of hTSC-organoids disrupted the stemness of hTSCs and the proliferation of cytotrophoblast cells (CTBs) and probably led to a preeclampsia (PE) phenotype. Overall, our results clearly demonstrate that hTSCs represent the major target cells of ZIKV, and a reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepen our understanding of the characteristics and consequences of ZIKV infection of hTSCs in early human embryos.

| S-EPMC10491779 | biostudies-literature

An ectopic enhancer restores CFTR expression through de novo chromatin looping.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-13 | GSE203560 | GEO