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ABSTRACT: Chromosomal instability in human trophoblast stem cells and placenta

PROVIDER: PRJNA1181850 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31220176_1.fastq.gz	Fastqsanger.gz
	SRR31220176_2.fastq.gz	Fastqsanger.gz
	SRR31220177_1.fastq.gz	Fastqsanger.gz
	SRR31220177_2.fastq.gz	Fastqsanger.gz
	SRR31220178_1.fastq.gz	Fastqsanger.gz

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Chromosomal instability in human trophoblast stem cells and placenta

Project description:Chromosomal instability in human trophoblast stem cells and placenta

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Chromosomal instability in human trophoblast stem cells and placenta

Project description:The human placenta, a unique tumor-like organ, is typically thought to exhibit rare aneuploidy associated with adverse pregnancy outcomes. Discrepancies in reported aneuploidy prevalence in placenta likely stem from limitations in modeling and the resolution of detection methods. Here, we used isogenic trophoblast stem cells (TSCs) derived from both naïve and primed human pluripotent stem cells (hPSCs) to reveal the spontaneous occurrence of aneuploidy, suggesting chromosomal instability (CIN) as an inherent feature of the trophoblast lineage. We identified potential pathways contributing to the occurrence and tolerance of CIN. These findings were further validated using single-cell multiome data from healthy human placentas, where we observed a high prevalence of heterogeneous aneuploidy across trophoblast cells. Despite extensive chromosomal abnormalities, TSCs maintained their proliferative and differentiation capacities, suggesting that CIN is a typical aspect of placental development. Our study challenges the traditional view of aneuploidy in the placenta and provides new insights into the role of CIN in normal placental function.

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Human primed and naïve PSCs are equally potent in differentiating into bona fide trophoblast stem cells (ATAC-Seq)

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Induction of human trophoblast stem-like cells from primed pluripotent stem cells

Project description:The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system has hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only comparable morphology and gene expression profile to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from pre-existing primed PSCs and provide a valuable opportunity to study human placenta development and pathology even from patients with placenta-related diseases.

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Project description:To understand the human placenta development, we investigated the features of two trophoblast models, trophoblast organoids and trophoblast stem cells, with the aim of identifying which type of trophoblast in vivo they most closely resemble. To this end, we profiled the transcriptomes from the two models by using the Truseq stranded mRNA library kit (Illumina).

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