Extended Data Fig. 4: KDM1A functions as a drug-induced AP gene by regulating differentiation. | Nature Genetics

Extended Data Fig. 4: KDM1A functions as a drug-induced AP gene by regulating differentiation.

From: Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer

Extended Data Fig. 4

a, Correlogram depicting Pearson correlation coefficients of KDM1A and RCOR1/2/3 depletion across nine drug modifier screens. Data from drug-modifier screens conducted in n = 2 biologically independent experiments. b, Immunoblot analysis of LSD1, MYC, H3K4me1 and H3K9me2 following CRISPR/Cas9 knockout of KDM1A in OCI-AML2 cells. Representative immunoblot of n = 3 independent experiments. Uncropped blots in Source Data. c, BH3 profiling of OCI-AML2 cells following CRISPR/Cas9 knockout of KDM1A versus non-targeting control. BCL2 priming defined as percent depolarization from HRK peptide (10μM) subtracted from percent depolarization from BAD (10μM) peptide. d,e, Flow-cytometry analysis of CD11b expression distribution (d) and median signal (e) in OCI-AML2 cells following CRISPR/Cas9 knockout of KDM1A versus non-targeting control. Median signal normalized to non-targeting control sgRNA. Data are mean ± SEM for n = 2 biologically independent experiments. f–i, BCL2 (f, h) and CD11b (encoded by ITGAM) (g, i) expression in hematopoietic stem cells (HSC; n = 11), common myeloid progenitors (CMP, n = 3), megakaryocyte-erythroid progenitor cell (MEP, n = 3), granulocyte monocyte progenitors (GMP, n = 3), CD11c+ myeloid dendritic cells (mDC, n = 5), CD123+ plasmacytoid dendritic cells (pDC, n = 5), and CD14+ monocytes (n = 13) from BloodSpot using HemaExplorer dataset. Sample size refers to biologically independent samples. Data are log2 expression of highest intensity microarray probe. Boxplot elements defined in Methods. c,f,g; P-values computed by two-sided two-sample t-Test for equal means. c,e,f,g; Data are mean ± SEM for n = 3 biologically independent experiments.

Source data

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