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

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

PROVIDER: PRJNA1106282 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28842511.fastq.gz	Fastqsanger.gz
	SRR28842512.fastq.gz	Fastqsanger.gz
	SRR28842513.fastq.gz	Fastqsanger.gz
	SRR28842514.fastq.gz	Fastqsanger.gz
	SRR28842515.fastq.gz	Fastqsanger.gz

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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]

2025-01-08 | GSE266193 | GEO

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 [ChIP-seq]

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

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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 [PBAT BS-Seq]

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

| PRJNA1106285 | ENA

Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development

Project description:Trophoblast organoids offer a unique opportunity to study mechanisms orchestrating placental growth and development during pregnancy. However, many organoid cultures rely on extracellular matrix reagents that are highly variable and unable to be tuned to reflect in vivo tissues. Here we describe the first bioprinted placental organoid model, generated using first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol matrix. Bioprinted organoids were compared comprehensively to classic Matrigel-embedding using functional assays, immunofluorescence microscopy, transcriptomic and proteomic analyses. Organoids differentiated spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs), with bioprinted organoids driven towards EVT differentiation. Bioprinted organoids were exposed to inflammation and treated with aspirin or metformin to assess their effects on trophoblast organoid formation and viability. Further, we reversed the inside-out architecture of ACH-3P organoids by suspension culture. Organoid suspension caused STBs to form a syndecan-1+ outer layer on the periphery of organoids, reflecting placental tissue. Here, we present an alternative trophoblast organoid model with further tuning potential to reflect the placental microenvironment in physiological and pathological pregnancies.

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Gene expression profiling of placental villi from intrauterine and tubal ectopic pregnancies

Project description:The tubal ectopic pregnancy (TEP) is a severe pregnancy complication accounted for 10-15% pregnancy-related deaths owing to the implantation and growth of embryos in fallopian tubes. Placental villi from TEP exhibit significant difference compared with that from intrauterine pregnancy (IP) in total volumes, trophoblast differentiation and intravillous vascularization. To investigate the difference in expression profiles of placental villi from IP and TEP, placental villi were collected from each phenotype, separated from maternal tissues and analyzed by high-throughput sequencing.

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

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

2025-01-08 | GSE266196 | GEO

Transcription profiling of placental trophoblast stem cells time dependent response to hyperosmolar stress

Project description:Stress induces undifferentiated stem cells to differentiate in a way that looks like normal differentiation; We used hyperosmolar stress as a generic, energy-depleting stressor and tested for the global changes in the transcriptional response of placental trophoblast stem cells Experiment Overall Design: Placental trophoblast stem cells were subjected to 0, 0.5, 2, 6, and 24 hours of hyperosmolar stress and then assayed by Affymetrix 430MOE V2 whole mouse genome arrays.

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