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. 2021 Jun 24;12:650977. doi: 10.3389/fimmu.2021.650977

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Copyright © 2021 Klein, Witalisz-Siepracka, Gotthardt, Agerer, Locker, Grausenburger, Knab, Bergthaler and Sexl

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Loss of CDK6 deregulates major cellular processes, including metabolic pathways and cytokine signaling in CD8+ T cells. (A) Splenic CD3+CD8+ T cells were sorted ex vivo from WT, Cdk6^- ^/- and Cdk6 ^K43M mice and lysed for RNA-sequencing. Three biological replicates (each pooled from two mice) were prepared per genotype. (B) The heatmap depicts genes significantly deregulated (FDR < 0.05, >1.25x fold change) in Cdk6^- ^/- vs. WT and Cdk6 ^K43M vs. WT CD8+ T cells. (C, D) Pathway analysis was performed using the Reactome Pathway tool with genes that were significantly upregulated (C) or downregulated (D) in Cdk6^- ^/- compared to WT CD8+ T cells. Significant pathways (FDR<0.05) are ranked by fold enrichment. Bar graphs show the top 20 upregulated non-redundant Reactome pathways in (C), while all downregulated significant non-redundant pathways are depicted in (D).