Extended Data Fig. 8: Screening of in silico predictions identifies successful hits and compounds that fail to drive predicted signatures. | Nature Neuroscience

Extended Data Fig. 8: Screening of in silico predictions identifies successful hits and compounds that fail to drive predicted signatures.

From: A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states

Extended Data Fig. 8

(A) Schematic overview of workflow for compound treatment. To explore the correct dosage for downstream studies, we conducted dose titration to examine viability of cells after treatment with varying dosages of our drugs. After choosing optimal concentrations, we conducted initial screening with qPCR to select candidates for final validation, then conducted final validation with bulk RNA-seq and proteomics. (B)-(D) qPCR results for different cluster families. Results not shown in Fig. 8b-d are shown here. Some compounds had effects on specific marker genes, but these did not pass our criteria for further study. Bars represent mean fold change expression, and error bars represent SD. All replicates are biological. Number of replicates per experiment as follows - Dorsomorphin: 6hrs: CXCR4 - n = 6, SRGN – n = 7; 24hrs: both n = 6, BX-795: 6hrs: CXCR4 - n = 5, SRGN – n = 8; 24hrs: CXCR4 - n = 3, SRGN – n = 5, BMS-2455421: 6hrs: both - n = 4; 24hrs: CXCR4 - n = 3, SRGN – n = 4, BRD: 6hrs: both - n = 7; 24hrs: TYROPB - n = 6, GPX1 – n = 7, Budesonide: 6hrs: n = 3; 24hrs: n = 3, Naltrexone: 6hrs: n = 3; 24hrs: n = 3, Cytochalasin b: 6hrs: SRGAP2 - n = 6, MEF2A – n = 5; 24hrs: both n = 6.

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