Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from undifferentiated human ES cell line, khES3 grown using complete, leucine or lysine deprived media

ABSTRACT: In undifferentiated human ES cells, 48hr Leucine deprivation (delta Leu) or Lysine deprivation (delta Lys) led to apoptosis. We used microarrays to detail the mollecular mechanism of cell-death caused by Leu, Lys deprivation in undifferentiated ES cells. Cells were harvested at undifferentiated stages for RNA extraction and hybridization on Affymetrix microarrays. We performed gene expression profiles of undifferentiated khES3 cells cultured in complete (comple),Leu or Lys deprivation for 5 hr.

ORGANISM(S): Homo sapiens

SUBMITTER: nobuaki shiraki

PROVIDER: E-GEOD-55284 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Skeletal muscle atrophy is dictated by the balance between protein synthesis and protein breakdown, known as proteostasis. With advanced age, muscle atrophy contributes to development of co-morbidities, loss of strength and independence, and all-cause mortality. Aging also coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence associated secretory phenotype. Previously, we found that a metformin + leucine (MET+LEU) combination treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy. Therefore, the objective of this study was to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence. C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during serum-deprivation (SD) atrophy. Single myofibers were isolated from aged (22-23 mo) C57Bl6/J mice, and human primary myoblasts were extracted from a healthy older adult donor. 25 + 125 µM MET+LEU treatment increased differentiation of myotubes and prevented SD induced atrophy. Low concentration (0.1 + 0.5 µM) MET+LEU had unique effects to prevent myotube atrophy and cause transcriptional reprogramming compared to individual therapies. SD increased inflammatory and cellular senescence pathways that was reversed with MET+LEU treatment. SD resulted in dysregulated proteostasis that was rescued with MET+LEU, and proteasome inhibition with MG-132 also rescued myotube atrophy. Cellular senescence transcriptional pathways and markers increased by SD were reversed with MET+LEU treatment, and dasatinib + quercetin (D+Q) senolytic treatment prevented myotube atrophy similar to MET+LEU. In aged myofibers, MET+LEU prevented SD atrophy, and in human primary myotubes MET+LEU prevented reductions in myonuclei fusion. These data provide evidence that MET+LEU has muscle cell intrinsic properties to prevent atrophy by reversing senescence and improving proteostasis

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Expression data from undifferentiated human ES cell line, khES3 grown using complete, leucine or lysine deprived media

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