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Series GSE248822 Query DataSets for GSE248822
Status Public on Feb 01, 2024
Title Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism I
Organism Homo sapiens
Experiment type Expression profiling by array
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.
 
Overall design We performed time-series gene expression profiling analysis in normal, human diploid fibroblasts (strain WI38) exposed to diverse forms of senescence-inducing stress including hyper-active RAS oncogene, replicative exhaustion (RS), and DNA damage (etoposide, i.e., DDIS). We confirmed these results in additional senescence models: SkMC human primary myoblasts undergoing RAS-OIS.

Source code and additional data accessible at: https://zenodo.org/records/8199751
 
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
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
Lab SENESCENCE, METABOLISM AND CARDIOVASCULAR DISEASES
Street address 8 rue du Général Sarrail
City CRETEIL
ZIP/Postal code 94010
Country France
 
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (63)
GSM7920621 MYOBLAST_SENESCENCE_TRANSCRIPTOME_RAS_168H_REP1
GSM7920622 MYOBLAST_SENESCENCE_TRANSCRIPTOME_RAS_168H_REP2
GSM7920623 MYOBLAST_SENESCENCE_TRANSCRIPTOME_RAS_240H_REP1
This SubSeries is part of SuperSeries:
GSE248824 Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism
Relations
BioProject PRJNA1046071

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Supplementary file Size Download File type/resource
GSE248822_RAW.tar 1.5 Gb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table
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