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This study used RNA-seq to investigate the transcriptome of primary monolayer KC cultures grown from lesional (PP) and non-lesional (PN) biopsies of psoriasis patients and control subjects (NN). Whole skin biopsies from the same subjects were evaluated concurrently. RNA-seq analysis of whole skin identified a larger number of psoriasis-increased differentially expressed genes (DEGs), but analysis of KC cultures identified more PP- and PN-decreased DEGs. These latter DEG sets overlapped more strongly with genes near loci identified by psoriasis genome-wide association studies and were enriched for genes associated with epidermal differentiation. Consistent with this, the frequency of AP-1 motifs was elevated in regions upstream of PN-KC-decreased DEGs. A subset of these genes belonged to the same co-expression module, mapped to the epidermal differentiation complex, and exhibited differentiation-dependent expression. These findings demonstrate a decreased differentiation gene signature in PP\/PN-KCs that had not been identified by pre-genomic studies of patient-derived monolayers. This may reflect intrinsic defects limiting psoriatic KC differentiation capacity, which may contribute to compromised barrier function in normal-appearing uninvolved psoriatic skin.<\/jats:p>","DOI":"10.1038\/s41598-017-18404-9","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T05:44:53Z","timestamp":1513575893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-6363","authenticated-orcid":false,"given":"William R.","family":"Swindell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinal K.","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianying","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymie","family":"Baliwag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Elder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann E.","family":"Gudjonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,22]]},"reference":[{"key":"18404_CR1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1146\/annurev-immunol-032713-120225","volume":"32","author":"MA Lowes","year":"2014","unstructured":"Lowes, M. 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