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Transitions in cell potency during early mouse development are driven by Notch

ABSTRACT: Transitions in cell potency during early mouse development are driven by Notch

PROVIDER: PRJNA501881 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8136670.fastq.gz	Fastqsanger.gz
	SRR8136671.fastq.gz	Fastqsanger.gz
	SRR8136672.fastq.gz	Fastqsanger.gz
	SRR8136673.fastq.gz	Fastqsanger.gz
	SRR8136674.fastq.gz	Fastqsanger.gz

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Transitions in cell potency during early mouse development are driven by Notch

Project description:The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.

2019-04-24 | GSE121979 | GEO

Transitions in cell potency during early mouse development are driven by Notch.

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Paneth cells acquire multi-potency upon Notch activation after irradiation

Project description:Paneth cells acquire multi-potency upon Notch activation after irradiation

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Human fetal kidney organoids model early human nephrogenesis and notch-driven cell fate

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Early Notch signaling programs effector CD8+ T cell differentiation [ATAC-Seq]

Project description:A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies to fight infections and cancer. Using genetic mouse models and blocking antibodies, we uncovered cellular and molecular mechanisms by which Notch signaling favors efficient generation of effector CD8+ T cells. Using transcriptional and epigenetic studies, we identified a unique Notch-driven T cell-specific signature. Early Notch signals were associated with chromatin opening in regions occupied by bZIP transcription factors, specifically BATF, known to be important for CD8+ T cell differentiation. Overall, we show that the delivery of early Notch signals controls the molecular and functional fate of CD8+ T cells after infection.

2025-02-21 | GSE289392 | GEO

Early Notch signaling programs effector CD8+ T cell differentiation [RNA-Seq]

2025-02-21 | GSE289394 | GEO

Chromatin architecture transitions from zebrafish sperm through early embryogenesis

Project description:Chromatin architecture transitions from zebrafish sperm through early embryogenesis

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Human fetal kidney organoids model early human nephrogenesis and notch-driven cell fate

Project description:Pluripotent stem cell–derived kidney organoids (PSC-KOs) have been put forward as a preferred culture system in which to study human kidney development and disease. In contrast, the development of human fetal kidney tissue–derived organoids (hFKOs) that could serve as a benchmark for PSC-KOs has not advanced very far. Herein, utilizing a chemically defined serum-free medium, we established a long-term culture protocol for hFKOs that self-organize into polarized renal epithelium and faithfully recapitulate nephrogenic and ureteric bud cell lineages. Bulk transcriptomics, single-cell RNA sequencing, and pseudotime analysis along with immunostaining revealed diverse populations among hFKOs, with a preserved differentiation axis mostly at higher levels and to a greater extent than for PSC-KOs. Accordingly, compared to PSC-KOs, hFKOs were significantly enriched for the NOTCH signaling pathway genes, allowing single-cell analysis of changes following NOTCH inhibition. We observed a preferential increase of mature distal tubules at the expense of early proximal tubules and defined a new adaptive prominin 1–expressing (PROM1+, or CD133+) cell state that escapes NOTCH inhibition to generate proximal and distal tubules. Overall, the concomitant understanding of developmental processes using hFKOs is a key development for the fields of kidney stem cell biology and regenerative medicine.

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NOTCH signaling pathway is required for bovine early embryonic development

Project description:The NOTCH signaling pathway plays an important role in regulating various biological processes, including cell proliferation, lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of NOTCH pathway in early embryonic development is poorly understood, especially in domestic animals. Here, we show that key transcripts of the NOTCH pathway exhibit a dynamic pattern throughout early embryonic development with an abundant level before embryonic genome activation in cattle. We also confirmed the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrated that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, we observed a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres in not only NOTCH1 depleted embryos but RBPJ depleted ones. Importantly, RNA-seq analysis revealed that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO also results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.

2021-01-31 | GSE158679 | GEO

NOTCH-driven oscillations control cell fate decisions during intestinal homeostasis

Project description:NOTCH-driven oscillations control cell fate decisions during intestinal homeostasis

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