Dataset Information

Evolutionary Trajectories of IDH-Mutant Astrocytoma Identify Molecular Grading Markers Related to Cell Cycling

ABSTRACT: To study the evolutionary processes that drive malignant progression of IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples using genetic, epigenetic, transcriptomic and proteomic profiling combined with single-cell analysis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Neoplastic Cell

DISEASE(S): Brain Cancer

SUBMITTER: Marcel Bühler

LAB HEAD: Tobias Weiss

PROVIDER: PXD062328 | Pride | 2025-07-08

REPOSITORIES: Pride

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			Action	DRS
	20210720_003_GLASSNL_LGGcontrol1_S307424.d.zip	Other
	20210720_004_GLASSNL_LGG1_S307425.d.zip	Other
	20210720_005_GLASSNL_LGG2_S307426.d.zip	Other
	20210720_006_GLASSNL_LGG3_S307427.d.zip	Other
	20210720_007_GLASSNL_LGG4_S307428.d.zip	Other

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Project description:In order to successfully survive in and to colonize the gastrointestinal tract, bacteria need to develop strategies to overcome bile acid stress. The most prominent bile acids are the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) as well as the secondary bile acid deoxycholic acid (DCA). In this study, we investigated the stress response of E. faecalis and E. faecium to sublethal concentrations of these three bile acids on the proteome level using DIA-MS. As both species showed similar IC50 for DCA and CDCA in growth experiments and both were highly resistant towards CA, we assumed similar changes to their protein expression profiles. Moreover, we investigated proteomic differences of E. faecalis grown under aerobic or microaerophilic conditions. Our findings showed similarities, but also species-specific variations in the response to the different bile acids, which reveal potential differences in the adaptation process. DCA and CDCA had a strong effect on down-expression of proteins involved in translation, transcription and replication in E. faecalis, but to a lesser extent in E. faecium. Proteins commonly significantly altered in their expression in all bile acid treated samples were identified for both species and represent a “general bile acid response”. Among these, ABC-transporters, multi-drug transporters and proteins related to cell wall biogenesis were up-expressed in both species and thus seem to play an essential role in bile acid resistance. Specific for all E. faecalis samples was the up-expression of several subunits of a V-type ATPase and the down-expression of proteins involved in pyruvate-, citrate- and folate metabolism. Most of the differentially expressed proteins were also identified when E. faecalis was incubated with low levels of DCA at microaerophilic conditions in comparison to aerobic conditions, indicating that adaptations to bile acids and to a microaerophilic atmosphere can occur simultaneously.

Dataset Information

Evolutionary Trajectories of IDH-Mutant Astrocytoma Identify Molecular Grading Markers Related to Cell Cycling

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