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RNA-seq to compare gene expression profiles between Asf1a WT and Asf1a KO cells

ABSTRACT: KrasG12D/P53-/-(KP)-Cas9 single clone was transfected with ctrl vector, ctrl sgRNA-1, ctrl-sgRNA-2 or ctrl-sgRNA-3 and then selected by using 5ug/ml Blasticidin, to get the 4 ctrl lines; KP-Cas9 single clone was transfected with Asf1a sgRNA-1, sgRNA-2, sgRNA-3 and new sgRNA-1 and then selected by using 5ug/ml Blasticidin, and then picked up single clones with Asf1a KO. For each Asf1a sgRNA, we selected one clone for RNA seq, so totally we have 4 Asf1a KO clones for RNA seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE127205 | GEO | 2019/11/26

REPOSITORIES: GEO

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In vivo epigenetic CRISPR screen identifies Asf1a as an immunotherapeutic target in Kras-mutant lung adenocarcinoma

Project description:Despite substantial progress in lung cancer immunotherapy, the overall response rate in KRAS-mutant lung adenocarcinoma (ADC) patients remains low. Combining standard immunotherapy with adjuvant approaches that enhance adaptive immune responsesâ€”such as epigenetic modulation of anti-tumor immunityâ€”is therefore an attractive strategy. To identify epigenetic regulators of tumor immunity, we constructed an epigenetic-focused sgRNA library, and performed an in vivo CRISPR screen in KrasG12D/P53-/- (KP) lung ADC model. Our data showed that loss of the histone chaperone Asf1a in tumor cells sensitizes tumors to anti-PD-1 treatment. Mechanistic studies revealed that tumor cell intrinsic Asf1a deficiency induced immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression and potentiated T cell activation in combination with anti-PD-1. Our results provide a rationale for a novel combination therapy consisting of Asf1a inhibition and anti-PD-1 immunotherapy.

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Genome-wide maps of chromatin state for HIRA, UBN1 and ASF1a

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Genome-wide maps of chromatin state for HIRA, UBN1 and ASF1a

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RNA-seq to compare gene expression profiles between Asf1a WT and Asf1a KO cells

Project description:RNA-seq to compare gene expression profiles between Asf1a WT and Asf1a KO cells

| PRJNA524337 | ENA

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