Cellular Genomic Maps Help Dissect Pathology in Human Skin Disease

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Cellular Genomic Maps Help Dissect Pathology in Human Skin Disease Asifa S. Haider, Michelle A. Lowes, Mayte Suàrez-Fariñas, Lisa C. Zaba, Irma Cardinale, Miroslav Blumenberg, James G. Krueger Journal of Investigative Dermatology Volume 128, Issue 3, Pages 606-615 (March 2008) DOI: 10.1038/sj.jid.5701067 Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Defining genes expressed in keratinocytes, fibroblasts, macrophages, monocytes, T cells, and immature and mature DCs. mRNA from cultured cells was hybridized to individual oligonucleotide arrays containing ~12,000 human genes (Affymetrix HG-U95Av2 chips). Heatmaps show unsupervised hierarchical clusters of upregulated genes in individual cell types (>1.5-folds compared with other cell types; P<0.05, n=2–4) using the similarity measure: Pearson's correlation. Areas of clusters in red for individual cell types define the number of upregulated cell lineage genes (number shown in parenthesis), compared with green areas with lower expressions of same genes (horizontally) in other cell types. (a) Lineage genes in keratinocytes, fibroblasts, macrophages, monocytes, T cells, and DCs. (b) DCs cluster: lineage DCs genes before (immature DCs) or after maturation (mature mDCs). (c) Examples of normalized gene expression corresponding to the cell types described in (a) and (b). The expressions of the representative cell lineage genes are 1.5-fold greater than in all other cell types (blue areas) (Tables S1A–6 list all genes). Journal of Investigative Dermatology 2008 128, 606-615DOI: (10.1038/sj.jid.5701067) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Common genes in cell groups. mRNA from cultured cells was hybridized to individual oligonucleotide arrays containing ~12,000 human genes (Affymetrix HG-U95Av2 chips). Heatmaps show unsupervised hierarchical clusters of upregulated genes in cell groups (>1.5-folds compared with other cell type; P<0.05, n=2–4) using the similarity measure: Pearson's correlation. Areas of clusters in red for individual cell groups define the number of upregulated cell lineage genes (number shown in parenthesis) compared with green areas with lower expressions of the same genes (horizontally) in other cell types. (a) Common myeloid cells (DCs, macrophages, and monocytes), b skin-resident cells (fibroblasts and keratinocytes) (c) leukocytes (monocytes, macrophages, DCs, and T cells), and d multiple cells (DCs, monocytes macrophages, T cells, fibroblasts, or keratinocytes). (b) Examples of normalized gene expressions of the cell groups described in (a). The expressions of the representative group lineage genes are 1.5-fold greater than in other cell types (blue areas) (Tables S7A–10 list all genes). Journal of Investigative Dermatology 2008 128, 606-615DOI: (10.1038/sj.jid.5701067) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Defining cell activation genes. mRNA from cultured cells was hybridized to individual oligonucleotide arrays containing ~12,000 human genes (Affymetrix HG-U95Av2 chips). Heatmaps show unsupervised hierarchical clusters of upregulated genes in activated cells (>1.2-fold compared with control; P<0.05, n=2) using the similarity measure: Pearson's correlation. Areas of clusters in red for activation genes define the number of upregulated genes (number shown in parenthesis) as compared with green areas with lower expressions of the same genes (horizontally) in controls. (a) Genes found in anti-CD3/CD28-treated T cells and PBMCs, (b) Venn diagram describes the number of unique and common genes in activated cells. (c) Examples of normalized gene expressions in activated T cells and PBMCs. Ratios of gene expressions of selected genes in each activated cell type compared with control are greater than 1.2-fold in treated versus control (P<0.05,n=2), ND=not detected. (Table S12A lists all genes). Journal of Investigative Dermatology 2008 128, 606-615DOI: (10.1038/sj.jid.5701067) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Lineage- and activation-specific genes: mRNA analysis with real-time RT-PCR from cultured monocytes (mono), immature DCs (iDC), mature DCs (mDC), T cells controls and after activation with anti-CD28/CD3 antibodies (T cell act.), fibroblasts (Fibro), keratinocytes (KC), and macrophages (Mac). (a) Genes expressed in resting and activated T cells: CD3D, lymphotoxin-α, and IFN-γ. (b) Genes expressed in resting and activated myeloid cells: CD11c, DCs-LAMP (LAMP 3) and indoleamine-pyrrole 2,3-dioxygenase (INDO). Mean of relative mRNA expression normalized to human acidic ribosomal protein (HARP) is plotted on column bars: SEM, n=2–4. Journal of Investigative Dermatology 2008 128, 606-615DOI: (10.1038/sj.jid.5701067) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Cytokines, chemokines, and proinflammatory genes in resting and activated cells in psoriasis. Black highlights describe the presence of the gene in the listed cell types. (+): activation genes in T cells (*): genes expressed in mature DCs. T: genes induced by TNF in keratinocytes. I: genes induced by IFN-γ in keratinocytes; IL-20: genes induced by IL-20 in keratinocytes. Grey highlight: genes uniquely expressed in activated cells. Journal of Investigative Dermatology 2008 128, 606-615DOI: (10.1038/sj.jid.5701067) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions