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. 2022 Jun 22;219(8):e20212477. doi: 10.1084/jem.20212477

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© 2022 Lemke and Huang

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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Figure 3. — The transcriptomic response of PAM versus M. marinum–associated macrophages. (A) Seven microglial cell clusters (c0–6) defining seven transcriptomic states in APP/PS1 Alzheimer’s mice, generated by Seurat analysis of single-cell RNA-seq results and displayed using uniform manifold approximation and projection (UMAP). Clusters 0 and 5 are the principal homeostatic (NPAM) and activated (PAM) clusters, respectively. Modified from Huang et al. (2021), with permission. (B) Comparative composite heatmaps for the indicated genes (mRNAs) across microglial transcriptomic clusters in APP/PS1 mice (as in A) and macrophage transcriptomic clusters in the M. marinum granuloma (as in Cronan et al. [2021]). X0Epi, X1Epi, etc. are epithelioid macrophages clusters, and X9Inf is the inflammatory macrophage cluster (Cronan et al., 2021). The differentially expressed genes shown are down-regulated in microglial state 5 (PAM) versus state 0 (NPAM), with the criteria of log(fold-change) >0.25 and adjusted P value <0.05. Columns are organized by similarity, based on unsupervised hierarchical clustering using the heatmap.2 function in R. Values shown as z-scaled log-transformed normalized average gene expression for each group. (C) The differentially expressed genes shown are up-regulated in microglial state 5 (PAM) versus state 0 (NPAM). Columns are organized by similarity, based on clustering. (D–F) Hierarchical clustered normalized expression of the indicated phagocytosis genes (D), lysosomal function genes (E), and cell motility genes (F) across microglial transcriptomic clusters in APP/PS1 mice and macrophage transcriptomic clusters in the M. marinum granuloma.