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Whereas the extent of such biliary fibrosis is a negative predictor of long-term transplant-free survival, the cellular phenotypes involved in the fibrosis are not well established. Using a rhesus rotavirus-induced mouse model of BA, we demonstrate significant expansion of a cell population expressing the putative stem\/progenitor cell marker, PROMININ-1 (PROM1), adjacent to ductular reactions within regions of periportal fibrosis. PROM1<jats:sup>positive (pos)<\/jats:sup> cells express <jats:italic toggle=\"yes\">Collagen-1\u03b11<\/jats:italic>. Subsets of PROM1<jats:sup>pos<\/jats:sup> cells coexpress progenitor cell marker CD49f, epithelial marker E-CADHERIN, biliary marker CYTOKERATIN-19, and mesenchymal markers VIMENTIN and alpha-SMOOTH MUSCLE ACTIN (\u03b1SMA). Expansion of the PROM1<jats:sup>pos<\/jats:sup> cell population is associated with activation of Fibroblast Growth Factor (FGF) and Transforming Growth Factor-beta (TGF\u03b2) signaling. <jats:italic toggle=\"yes\">In vitro<\/jats:italic> cotreatment of PROM1-expressing <jats:italic toggle=\"yes\">Mat1a\u2212\/\u2212\n                                 <\/jats:italic> hepatic progenitor cells with recombinant human FGF10 and TGF\u03b21 promotes morphologic transformation toward a myofibroblastic cell phenotype with increased expression of myofibroblastic genes <jats:italic toggle=\"yes\">Collagen-1\u03b11<\/jats:italic>, <jats:italic toggle=\"yes\">Fibronectin<\/jats:italic>, and <jats:italic toggle=\"yes\">\u03b1-Sma<\/jats:italic>. Infants with BA demonstrate similar expansion of periportal PROM1<jats:sup>pos<\/jats:sup> cells with activated Mothers Against Decapentaplegic Homolog 3 (SMAD3) signaling in association with increased hepatic expression of <jats:italic toggle=\"yes\">FGF10<\/jats:italic>, <jats:italic toggle=\"yes\">FGFR1<\/jats:italic>, and <jats:italic toggle=\"yes\">FGFR2<\/jats:italic> as well as mesenchymal genes <jats:italic toggle=\"yes\">SLUG<\/jats:italic> and <jats:italic toggle=\"yes\">SNAIL<\/jats:italic>. Infants with perinatal subtype of BA have higher tissue levels of <jats:italic toggle=\"yes\">PROM1<\/jats:italic> expression than those with embryonic subtype. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Expansion of collagen-producing PROM1<jats:sup>pos<\/jats:sup> cells within regions of periportal fibrosis is associated with activated FGF and TGF\u03b2 pathways in both experimental and human BA. PROM1<jats:sup>pos<\/jats:sup> cells may therefore play an important role in the biliary fibrosis of BA. (Hepatology 2014;60:941\u2013953)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.27203","type":"journal-article","created":{"date-parts":[[2014,5,3]],"date-time":"2014-05-03T15:52:46Z","timestamp":1399132366000},"page":"941-953","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":46,"title":["Expansion of prominin-1-expressing cells in association with fibrosis of biliary atresia"],"prefix":"10.1097","volume":"60","author":[{"given":"Nirmala","family":"Mavila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavkumar","family":"Shivakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie V.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Utley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Mak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Vendyres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Groff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinji","family":"Asahina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper S.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-22-20250207","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1002\/hep.22001","article-title":"Corticosteroid treatment in biliary atresia: tonic or toast?","volume":"46","author":"Sokol","year":"2007","journal-title":"Hepatology"},{"key":"R2-22-20250207","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/SLA.0b013e3182300950","article-title":"The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplantfree survival.","volume":"254","author":"Superina","year":"2011","journal-title":"Ann Surg"},{"key":"R3-22-20250207","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00428-011-1048-3","article-title":"Ductal plates in hepatic ductular reactions. 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