{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:41:59Z","timestamp":1790775719968,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fibroblasts interact with keratinocytes and melanocytes to maintain skin homeostasis. However, the impact of selective melanocyte loss on the transcriptome of fibroblasts is not fully understood. Thus, we sought to understand the genome\u2010wide transcriptome of fibroblasts derived from non\u2010lesional (NL) and lesional (L) dermis in patients with non\u2010segmental vitiligo. Transcriptional profiling of NL and L fibroblasts was performed on three individuals with vitiligo using next\u2010generation\u2010sequencing. Functional protein\u2013protein interaction (PPI) networks were constructed for the significantly upregulated and downregulated genes, as well as for a common set of genes that were downregulated in both fibroblasts and epidermis in L skin (identified previously). Proliferation potential of NL and L fibroblasts was assessed experimentally. Genome\u2010wide transcriptome analysis revealed a total of 414 (282, downregulated; 132, upregulated) differentially expressed (DE)\u2010transcripts in L as compared to NL fibroblasts. Unsupervised hierarchical clustering of DE\u2010transcripts segregated L and NL fibroblasts into two distinct clades, despite the apparent heterogeneity in lesions of different vitiligo patients. Gene Ontology analysis of downregulated genes revealed enrichment of keratinocyte\u2010specific biological processes such as cornification and keratinization. PPI networks constructed for the downregulated and upregulated genes revealed deregulation of several hub genes associated with cell cycle regulation and cAMP metabolism respectively. Similarly, the PPI networks constructed for 67 genes downregulated in both fibroblasts as well as epidermis of L skin revealed downregulation of hub genes including stratifin, PIK3CG and CDH1. Analysis of the in vitro proliferation potential of L fibroblasts revealed a decrease in the expression of proliferation markers Ki67, MCM6, pERK and pCDK2, a decreased S phase population and an increase in alpha\u2010SMA and collagen expression, corroborating the downregulation of hub genes associated with proliferation identified by PPI network analysis. Our study revealed pervasive transcriptional alterations in L compared to NL fibroblasts in vitiligo. The PPI analysis suggested a reduced potential to proliferate in melanocyte\u2010deprived lesional fibroblasts, which was validated experimentally as well.<\/jats:p>","DOI":"10.1111\/exd.14702","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T05:50:36Z","timestamp":1667627436000},"page":"331-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genome\u2010wide profiling reveals pervasive transcriptional alterations in fibroblasts derived from lesional skin in vitiligo including a reduced potential to proliferate"],"prefix":"10.1111","volume":"32","author":[{"given":"Rohit","family":"Gupta","sequence":"first","affiliation":[{"name":"Skin Biology Laboratory CSIR\u2010Institute of Genomics and Integrative Biology  New Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachita","family":"Misri","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hindu Rao Hospital  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aayush","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre Dr. D.Y. Patil Vidyapeeth  Pune Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Skin Biology Laboratory CSIR\u2010Institute of Genomics and Integrative Biology  New Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-9489","authenticated-orcid":false,"given":"Archana","family":"Singh","sequence":"additional","affiliation":[{"name":"Skin Biology Laboratory CSIR\u2010Institute of Genomics and Integrative Biology  New Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10253-w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000000171"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2007.00385.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12798"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30614"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118722"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700014"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15651"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12985"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-016-1713-0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.06.033"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2013.22.8.407"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700629"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03592-0"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051040"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020119"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20782"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.62"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4104"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80595-4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23765.x"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14702","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/exd.14702","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.14702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:09:25Z","timestamp":1692691765000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.14702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/exd.14702"],"URL":"https:\/\/doi.org\/10.1111\/exd.14702","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]},"assertion":[{"value":"2022-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}