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MRNA-seq to test effect of PYK2 inhibitor (defactinib) on LPS induced gene expression in WT and IRF5-/- BMDMs

ABSTRACT: To investigate the specificity of Defactinib on IRF5 target genes we compare LPS-induced transcriptomes in WT and IRF5 KO BMDMs treated with either Defactinib or vehicle. Macrophage transcriptomic signature under PYK2 inhibition phenocopied IRF5 deficiency

ORGANISM(S): Mus musculus

PROVIDER: GSE141082 | GEO | 2021/10/22

REPOSITORIES: GEO

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mRNA-seq to test effect of PYK2 inhibitor (defactinib) on LPS induced gene expression in WT and IRF5-/- BMDMs

Project description:mRNA-seq to test effect of PYK2 inhibitor (defactinib) on LPS induced gene expression in WT and IRF5-/- BMDMs

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Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner

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Genome-wide maps of chromatin state of IRF5+/+ and IRF5-/- CD4+ mouse T cells

Project description:Genetic variants in IRF5 are associated with multiple immune-mediated diseases. IRF5 has been predominantly focused on for its regulation of myeloid-derived cells. We found that IRF5 contributes to CD4+ T cell outcomes and that it regulates early T cell receptor-initiated signaling and subsequently translocates to the nucleus where it binds to promoters of various genes regulated with T cell activation. We report the chromatin state of freshly isolated and activated IRF5+/+ and IRF5-/- CD4+ T cells in vitro. While there are minimal differential peaks between freshly isolated IRF5+/+ and IRF5-/- CD4+ T cells, once activated multiple differential peaks are observed between IRF5+/+ and IRF5-/- CD4+ T cells.

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Kinetics of LPS induction in wt and Cop1-ko BMDMs

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Project description:Cancer stem cells (CSCs) are implicated in tumor initiation, metastasis and drug resistance, and are considered as attractive targets for cancer therapy. We identified a clinically relevant signaling nexus mediated by PYK2 and its impact on stemness in triple negative breast cancer (TNBC). PYK2 depletion in multiple mesenchymal TNBC cell lines markedly reduced the expression of PKCα and AXL proteins and reduced the number of mammosphere-forming cells and cells harboring CSCs characteristic markers. PYK2 and PKCα cooperate at a convergence point of multiple stemness-inducing pathways to regulate AXL levels and concomitantly the levels/activation of key transcription factors implicated in stemness including STAT3, TAZ, FRA1 and SMAD3 as well as the pluripotent transcription factors Nanog and Oct4, and in-turn affect their target genes. Targeting the AXL-PYK2-PKCα circuit could be a promising strategy to eliminate CSCs in TNBC and possibly overcome drug resistance.

2021-03-26 | GSE166609 | GEO

Bone Marrow Derived Macrophages(BMDMs) transcriptome analysis of control, LPS and LPS plus BHB group

Project description:Purpose: The purpose of this study was to compare the BMDMs transcriptome in the control LPS and LPS plus BHB group in order to identify the critical pathway that contributed to the inhibiton of BHB on M1 polarization. Methods: 1× 106 BMDMs were pre-treated with PBS or BHB for 1 hours before LPS administration. Four hours later, BMDMs were harvested for RNA preparation. Results: Among 16650 mapped genes, 7325 differentially expressed genes were identified, including 244 LPS inducible BHB down regulated named class A and 537 LPS repressed BHB up regulated genes named class B. The genes in class A were mainly TLR4 and TNF signaling pathway, while genes in class B were associated with negative regulation of transcription and NF-KB signaling. The GSEA showed that BHB have the similar profiles chnage on BMDMs with TSA. Conclusions: Our study revealed that BHB down regulated TLR4 and NF-KB pathway related genes to inhibited M1 polarization, and BHB have a similar effect on BMDMs with TSA through comparing the genetic changes of two substance caused in cells.

2022-04-06 | GSE152241 | GEO

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