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Netrin-1 signalling function in mouse pluripotent stem cells

ABSTRACT: Netrin-1 signalling function in mouse pluripotent stem cells

PROVIDER: PRJNA399081 | ENA |

REPOSITORIES: ENA

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Netrin-1 signalling function in mouse pluripotent stem cells [ChIP-Seq]

Project description:Netrin-1 signalling function in mouse pluripotent stem cells [ChIP-Seq]

| PRJNA414537 | ENA

Netrin-1 signalling function in mouse pluripotent stem cells [RRBS]

Project description:We describe here the consequences of the activation of the netrin-1 signalling pathway in mouse embryonic stem cells (mESC).

2019-12-02 | GSE102829 | GEO

Netrin-1 signalling function in mouse pluripotent stem cells [ChIP-Seq]

Project description:We describe here the consequences of the activation of the netrin-1 signalling pathway in mouse embryonic stem cells (mESC).

2019-12-02 | GSE105062 | GEO

Netrin-1 signalling function in mouse pluripotent stem cells [RNA-seq]

Project description:We describe here the consequences of the activation of the netrin-1 signalling pathway in mouse embryonic stem cells (mESC).

2019-12-02 | GSE102826 | GEO

Netrin-1 signalling function in mouse pluripotent stem cells

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

2019-12-02 | GSE102831 | GEO

Mus musculus

Project description:Netrin-1 signalling function in mouse pluripotent stem cells [RRBS]

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Netrin-1 facilitates somatic cell reprogramming by limiting Dcc pro-apoptotic activity.

Project description:The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. However, the relative flaws in the understanding of the molecular mechanisms promoting or limiting reprogramming still hinder the efficient generation of high quality iPS cells. Whereas modulation of the initial Oct4, Sox2, Klf4 and c-Myc (OSKM) cocktail with new transcription factors has been extensively documented, comparatively little is known about soluble molecules promoting the process, even if such recombinant factors could be highly valuable for therapeutic applications. In this study we developed a large-scale identification method to uncover novel programmed cell death (PCD)-related mechanisms limiting somatic cell reprogramming to pluripotency (SCRP). We identified Netrin-1 and its dependence receptor Dcc (Deleted in Colorectal Carcinoma), previously described for their respective survival/death functions both in normal and oncogenic contexts, as novel key SCRP modulators. We show that the early phase of SCRP is accompanied with a strong Netrin-1 deficiency, due to the improper epigenetic regulation of the Ntn1 promoter by OSKM. Mechanistically, we demonstrate that such Netrin-1 imbalance induces apoptosis mediated by the dependence receptor Dcc in a p53-independent manner. Correction of the Netrin-1/Dcc equilibrium by gain-of-ligand and loss-of-receptor experiments constrains apoptosis and improves reprogramming. As a consequence, we propose a novel iPS derivation protocol including a sequential treatment with recombinant Netrin1 that greatly facilitates the generation of mouse and human iPS cells. RNA-sequencing of mouse embryonic fibroblasts (passage 2 and passage 4), mouse pre-iPS cells (passage 5 and passage 25), 1 clone of control iPS (passage 5 and passage 25) and 2 independent clones of "Netrin-1 derived" iPS cells (passage 5 and passage 25). For this analysis, mouse iPS cell lines were grown in KSR+LIF media.

2015-09-01 | E-GEOD-54107 | biostudies-arrayexpress

Mus musculus

Project description:Netrin-1 signalling function in mouse pluripotent stem cells [RNA-seq]

| PRJNA400274 | ENA

A Floor Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist

Project description:Floor plate-derived extracellular signaling molecules, including canonical axon guidance cues of the Netrin family, control neuronal circuit organization. Despite the importance of the floor plate as an essential signaling centre in the developing vertebrate central nervous system, no systematic approach to identify binding partners for floor plate-expressed cellsurface and secreted proteins has been carried out. Here, we used a high-throughput assay to discover extracellular protein-protein interactions, which likely take place in the zebrafish floor plate microenvironment. The assembled floor plate network contains 47 interactions including the hitherto not reported interaction between Netrin-1 and Draxin. We further characterized this interaction, narrowed down the binding interface, and demonstrated that Draxin competes with Netrin receptors for binding to Netrin-1. Our results suggest that Draxin functions as an extracellular Netrin signaling modulator in vertebrates. A reciprocal gradient of Draxin might shape or sharpen the active Netrin gradient, thereby critically modulating its effect.

2015-05-31 | E-MTAB-3609 | biostudies-arrayexpress

Cell-surface proteomics identifies differences in signalling and adhesion protein expression between naive and primed human pluripotent stem cells

Project description:Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1700 plasma membrane proteins including those involved in cell adhesion, signalling and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signalling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signalling pathway activity and has identified new markers to define human pluripotent states.

2020-04-17 | PXD015359 | Pride

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