Project description:Amino acid availability is a crucial factor for survivability of cancer cells. Leukemia cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. Inhibition of GSK3a halts the sourcing of amino acids, which subsequently leads to cancer cell vulnerability towards asparaginase therapy. Leveraging RNA sequencing we show that GSK3a inhibition leads to temporally dynamic downregulation of distinct ribosomal proteins upon amino acid starvation.

2023-09-13 | GSE234800 | GEO

Asparagine availability controlsgerminal centre B cell homeostasis

Project description:Germinal centre (GC) B cells proliferate at some of the highest rates of any mammalian cell. Yet the metabolic processes which enable this are poorly understood. We performed integrated metabolomic and transcriptomic profiling of GC B cells, and found that asparagine metabolism is highly upregulated. Asparagine is conditionally essential to B cells, and its synthetic enzyme, asparagine synthetase (ASNS) is markedly upregulated following their activation, through the integrated stress response sensor general control non-derepressible 2 (GCN2). When Asns is deleted, B cell survival in low asparagine conditions is severely impaired. Using stable isotope tracing, we found that metabolic adaptation to the absence of asparagine requires ASNS, and that the synthesis of nucleotides is particularly sensitive to asparagine deprivation. Conditional deletion of Asns in B cells selectively impairs GC formation, associated with a reduction in RNA synthesis rates. Finally, removal of environmental asparagine by asparaginase was found to also severely compromise the GC reaction.

2024-04-03 | GSE228845 | GEO

Differentially expressed genes following ARID1A depletion

Project description:Differentially expressed genes following ARID1A depletion

| PRJNA477786 | ENA

Effect of asparagine depletion on Rspo3 fusion positive colorectal cancer cell organoid transcriptomes

Project description:Amino acid availability is a crucial factor for survivability of cancer cells. Colorectal cancer cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. Inhibition of GSK3a halts the sourcing of amino acids, which subsequently leads to cancer cell vulnerability towards asparaginase therapy. Leveraging RNA sequencing we show that GSK3a inhibition leads to a significant enrichment of ribosomal transcripts amongst transcripts that are differentially downregulated in asparaginase treated Rspo3 fusion positive colorectal cancer cell organoids.

2023-09-13 | GSE234801 | GEO

RNA expression following TMPRSS11B overexpression or depletion

Project description:RNA expression following TMPRSS11B overexpression or depletion

| PRJNA473063 | ENA

Asparagine starvation on histone methylation and gene expression

Project description:We are determining the impact of asparagine starvation on histone H3K4 trimethylation deposition across the genome and how they may affect the gene expression.

2022-06-16 | GSE206112 | GEO

Gene expression analysis following depletion of LOXL2 in esophgeal cancer cells

Project description:Gene expression analysis following depletion of LOXL2 in esophgeal cancer cells

| PRJNA559146 | ENA