{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:48:00Z","timestamp":1785422880754,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,23]]},"group-title":"Cell Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01ES017014"],"award-info":[{"award-number":["R01ES017014"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["P30AR069589"],"award-info":[{"award-number":["P30AR069589"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  In humans, 2,3,7,8-tetrachlorodibenzo-\n                  <jats:italic>p<\/jats:italic>\n                  -dioxin (TCDD) induces chloracne, a skin condition that presents with acanthosis, hyperkeratosis, comedones, and sebaceous gland (SG) atrophy (seboatrophy). Although chloracne-like phenotypes have been reported in TCDD-treated mice, the underlying mechanisms remain poorly understood. Previous studies showed that TCDD-induced CYP1A1 protein is expressed in LRIG1+ progenitor cells in hair follicles, suggesting that TCDD targets specific cell populations within the pilosebaceous unit. To explore the effects of TCDD on the epidermis and pilosebaceous unit, we analyzed single-cell RNA expression in wild-type and\n                  <jats:italic>Ahr<\/jats:italic>\n                  -null mice at postnatal day 21 (P21) following\n                  <jats:italic>in utero<\/jats:italic>\n                  and lactational exposure. The results showed that TCDD preferentially induced the AHR target genes\n                  <jats:italic>Cyp1a1<\/jats:italic>\n                  and\n                  <jats:italic>Cyp1b1<\/jats:italic>\n                  in the lower infundibulum and subjacent junctional zone overlapping the LRIG1+ progenitor cell niche. TCDD also caused\n                  <jats:italic>Ahr<\/jats:italic>\n                  -dependent seboatrophy, accompanied by increased expression of\n                  <jats:italic>Blimp1<\/jats:italic>\n                  , a transcriptional repressor that regulates SG size. A second site of\n                  <jats:italic>Cyp1a1<\/jats:italic>\n                  induction was the SG, where\n                  <jats:italic>Cyp1a1<\/jats:italic>\n                  was markedly elevated in the basal proliferating cells and immature sebocytes. In a 3-day topical exposure study of early effects, TCDD produced a dose-dependent increase of\n                  <jats:italic>Cyp1a1<\/jats:italic>\n                  expression in the SG that included the more differentiated sebocytes. This response was accompanied by expansion of the\n                  <jats:italic>Scd1<\/jats:italic>\n                  -positive area, elevated Nile Red lipid staining, and an increased number of\n                  <jats:italic>Blimp1<\/jats:italic>\n                  -high sebocytes, demonstrating that TCDD enhanced SG differentiation and lipid production\n                  <jats:italic>in vivo<\/jats:italic>\n                  . These changes preceded the onset of\n                  <jats:italic>Ahr<\/jats:italic>\n                  -dependent seboatrophy, providing new insight into the cellular and molecular events underlying chloracne pathogenesis.\n                <\/jats:p>","DOI":"10.64898\/2026.07.22.740060","type":"posted-content","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:00:15Z","timestamp":1784822415000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-cell analysis of 2,3,7,8-tetrachlorodibenzo-\n                  <i>p<\/i>\n                  -dioxin (TCDD)-treated murine skin demonstrates that sebaceous gland differentiation precedes\n                  <i>Ahr<\/i>\n                  -dependent seboatrophy with elevated expression of infundibular\n                  <i>Blimp1<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6335-5904","authenticated-orcid":false,"given":"Syeda Mashnia","family":"Tasnim","sequence":"first","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-6732","authenticated-orcid":false,"given":"Subhash","family":"Solanki","sequence":"additional","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-9584","authenticated-orcid":false,"given":"Jyoti","family":"Bhuju","sequence":"additional","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0688-6485","authenticated-orcid":false,"given":"Lauren","family":"Thompson","sequence":"additional","affiliation":[{"name":"Lauren Thompson, Integrated Microscopy Center, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9356-3918","authenticated-orcid":false,"given":"Omar","family":"Skalli","sequence":"additional","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA"},{"name":"Lauren Thompson, Integrated Microscopy Center, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-2200","authenticated-orcid":false,"given":"Elizabeth A.","family":"Grice","sequence":"additional","affiliation":[{"name":"Elizabeth A. Grice, Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6088-6320","authenticated-orcid":false,"given":"Carrie Hayes","family":"Sutter","sequence":"additional","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-7975","authenticated-orcid":false,"given":"Thomas R.","family":"Sutter","sequence":"additional","affiliation":[{"name":"Syeda Mashnia Tasnim, Department of Biological Sciences, University of Memphis, Memphis, TN 38152, 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