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NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence

ABSTRACT: NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence

PROVIDER: PRJNA293985 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2184380.fastq.gz	Fastqsanger.gz
	SRR2184390.fastq.gz	Fastqsanger.gz
	SRR2184400.fastq.gz	Fastqsanger.gz
	SRR2184410.fastq.gz	Fastqsanger.gz
	SRR2184420.fastq.gz	Fastqsanger.gz

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NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence

Project description:Senescence, a persistent form of cell cycle arrest, is often associated with a diverse secretome, which provides complex downstream functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence (OIS) is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-β-rich secretome, whilst suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPβ. NOTCH1 and NOTCH1-driven TGF-β contribute to ‘lateral induction of senescence’ through a juxtacrine NOTCH-JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo. Because enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared to typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-β and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition.

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NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence [N1ICD]

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NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence [CSM]

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Project description:NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence [CSM]

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NOTCH1 mediates a reciprocal switch between two distinct secretomes during senescence

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

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NOTCH1 mediates a switch between two distinct secretomes during senescence.

Project description:Senescence, a persistent form of cell-cycle arrest, is often associated with a diverse secretome, which provides complex functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-β-rich secretome, while suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPβ. NOTCH1 and NOTCH1-driven TGF-β contribute to 'lateral induction of senescence' through a juxtacrine NOTCH-JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo. As enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared with typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-β and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition.

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