A TAR transcriptional signature occurs in stressed keratinocytes from human inflammatory skin diseases (complement to Fig 8).

<p><b>(A)</b> Strategy for (i) devising a TAR-related signature from analyses of RNAseq data in dual TPATx mouse skin and (ii) harmonizing it with the human transcriptome using an existing data set from individuals with psoriasis (PSOR) [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.ref055" target="_blank">55</a>] (see Methods). The set of 441 genes significantly up-regulated (>8-fold; adj <i>P</i> < 0.01) in WT, but not in <i>Krt17-/-</i>, mouse skin 6 h after dual TPA Tx (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.g002" target="_blank">Fig 2I</a>) were designated as K17-dependent TAR genes; 209 homologs were identified in the PSOR data set [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.ref055" target="_blank">55</a>], forming the basis for a “TAR209” score, and 11 of these 209 genes are expressed at significant levels in PSOR keratinocytes, as opposed to other cell types (see B and C), forming the basis for the TAR11 composite score. <b>(B)</b> Expression of the “TAR209” score in specific cell clusters within the PSOR data set [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.ref055" target="_blank">55</a>]. <b>(C)</b> Expression of the “TAR11” score, which is based on the 11 genes showing higher expression levels in keratinocytes within the PSOR data set (<i>ANGPTL4</i>, <i>IFITM1</i>, <i>IFI16</i>, <i>PHLDA2</i>, <i>KLK1</i>, <i>PDPN</i>, <i>AKR1B10</i>, <i>ACAT2</i>, <i>TUBB6</i>, <i>OAS1</i>, <i>HRH2</i>), in different cell clusters in this data set. <b>(D)</b> Distribution of TAR11 scores in all individual cells from the AD single cell data set [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.ref064" target="_blank">64</a>]. <b>(E, F)</b> Violin plots reporting on the expression levels of <i>KRT6A</i> (E) and <i>KRT17</i> (F) in cells showing high, medium, and low TAR11 scores. Cut-offs were arbitrarily set at the 95th percentile for a high TAR score and at the 75th percentile for a medium TAR score based on the distributions shown in (D). <b>(G, I)</b> Sections of WT and <i>Krt17-/-</i> mouse ear skin collected 6 h after double TPA Tx (24 h apart) were immunostained for Histamine receptor H2 (HRH2) (G) or 2’-5’-Oligoadenylate Synthetase 1 (OAS1) (I). Scale bars: 50 μm. Dashed lines depict the dermo-epidermal interface. <b>(H, J)</b> Quantitation of the signal for HRH2 (H) or OAS1 (J) levels in epidermis from G or I. <i>n</i> = 3 mice. Data are shown as mean ± SEM. One-way ANOVA. The source data used to derive the numerical values reported here can be found in <b><a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.s016" target="_blank">S1 Data</a></b>.</p> <p>(PDF)</p>