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| Status |
Public on Feb 01, 2024 |
| Title |
Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism II |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cellular senescence impacts many physiological and pathological processes. A durable cell cycle arrest, inflammatory secretory phenotype, and metabolic reprogramming characterize it. Identifying common and specific metabolic liabilities in senescence provide novel inroads to exploit senescence targeting for health benefits. Here, we use dynamic transcriptome and metabolome profiling in different senescence subtypes to reveal common and specific metabolic signatures. Specifically, we pinpoint the homeostatic switch of glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation, intimately linking lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2- Ethanolamine (PCYT2) regulate this metabolic switch, which is senogenic. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn is senomorphic. Collectively, our study ties the G3P-PEtn homeostatic switch to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential, novel therapeutic avenue for senescence targeting in pathophysiology.
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| Overall design |
We performed time-series gene expression profiling analysis in normal, human diploid fibroblasts (strain WI38) undergoing senescence after exposition to either DNA Damage (DDIS) or RAS-oncogene overexpression (RAS-OIS). We administered the mTOR inhibitor Rapamycin, an established senomorphic, to WI38 cells undergoing DDIS, and Dimethyloxalylglycine (DMOG), a hypoxia-mimetic and competitive alphaKG antagonist to cells undergoing RAS-OIS. Total RNA was collected at the time points indicated and global gene expression levels were determined using Affymetrix HTA2.0 microarrays.
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| Contributor(s) |
Tighanimine K, Nabuco Leva Ferreira Freitas JA, Nemazanyy I, Bankolé A, Benarroch-Popivker D, Brodesser S, Doré G, Robinson L, Benit P, Ladraa S, Bou Saada Y, Friguet B, Bertolino P, Bernard D, Canaud G, Rustin P, Gilson E, Bischof O, Fumagalli S, Pende M |
| Citation(s) |
38409325 |
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| Submission date |
Nov 28, 2023 |
| Last update date |
Mar 07, 2024 |
| Contact name |
José Américo Nabuco Leva Ferreira Freitas |
| Organization name |
Institut Mondor de Recherche Biomedicale
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| Lab |
SENESCENCE, METABOLISM AND CARDIOVASCULAR DISEASES
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| Street address |
8 rue du Général Sarrail
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| City |
CRETEIL |
| ZIP/Postal code |
94010 |
| Country |
France |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (20)
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| GSM7920684 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D00_REP1 |
| GSM7920685 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D00_REP2 |
| GSM7920686 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D07_REP1 |
| GSM7920687 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D07_REP2 |
| GSM7920688 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D14_REP1 |
| GSM7920689 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_D14_REP2 |
| GSM7920690 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_RAPAMYCIN_D07_REP1 |
| GSM7920691 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_RAPAMYCIN_D07_REP2 |
| GSM7920692 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_RAPAMYCIN_D14_REP1 |
| GSM7920693 |
WI38_RNA_PHARM_INHIB_ETOPOSIDE_RAPAMYCIN_D14_REP2 |
| GSM7920694 |
WI38_RNA_PHARM_INHIB_RAS_D00_REP1 |
| GSM7920695 |
WI38_RNA_PHARM_INHIB_RAS_D00_REP2 |
| GSM7920696 |
WI38_RNA_PHARM_INHIB_RAS_D04_REP1 |
| GSM7920697 |
WI38_RNA_PHARM_INHIB_RAS_D04_REP2 |
| GSM7920698 |
WI38_RNA_PHARM_INHIB_RAS_D07_REP1 |
| GSM7920699 |
WI38_RNA_PHARM_INHIB_RAS_D07_REP2 |
| GSM7920700 |
WI38_RNA_PHARM_INHIB_RAS_DMOG_D04_REP1 |
| GSM7920701 |
WI38_RNA_PHARM_INHIB_RAS_DMOG_D04_REP2 |
| GSM7920702 |
WI38_RNA_PHARM_INHIB_RAS_DMOG_D07_REP1 |
| GSM7920703 |
WI38_RNA_PHARM_INHIB_RAS_DMOG_D07_REP2 |
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| This SubSeries is part of SuperSeries: |
| GSE248824 |
Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism |
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| Relations |
| BioProject |
PRJNA1046072 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248823_RAW.tar |
489.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Raw data provided as supplementary file |
| Processed data included within Sample table |
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