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However, the mechanisms governing BPPCs re-differentiation, particularly the role of non-parenchymal cells, remain poorly understood. Here, using a zebrafish model of extreme hepatocyte ablation, we demonstrate that platelet-derived growth factor (PDGF) ligands are rapidly induced in BPPCs and bind to Pdgfra on neighboring hepatic stellate cells (HSCs). Genetic inactivation or dominant-negative inhibition of pdgfra impairs HSC expansion and reduces HSC-derived midkine a (Mdka) expression, thereby limiting the re-differentiation of BPPCs into hepatocytes. Notably, heat-shock-induced mdka overexpression partially rescues the regenerative defect. Together, our findings identify a BPPC\u2013HSC paracrine feedback loop mediated by the PDGF\u2013Pdgfra\u2013Mdka axis that is essential for biliary-mediated liver regeneration. Targeting this axis may provide a therapeutic strategy for end-stage liver diseases.<\/jats:p>","DOI":"10.1242\/dev.205270","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:43:52Z","timestamp":1772009032000},"source":"Crossref","is-referenced-by-count":3,"title":["PDGF signaling drives bipotential progenitor cell re-differentiation during zebrafish biliary-mediated liver regeneration"],"prefix":"10.1242","volume":"153","author":[{"given":"Jieqiong","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofei","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfei","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]},{"name":"School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University 2 State Key Laboratory of Genetics and Development of Complex Phenotypes , , Shanghai 200438 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghui","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Southwest University 1 , Chongqing 400715 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-0510","authenticated-orcid":false,"given":"Jianlong","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University 2 State Key Laboratory of Genetics and Development of Complex Phenotypes , , Shanghai 200438 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"2026090107140722700_DEV205270C1","doi-asserted-by":"publisher","first-page":"103989","DOI":"10.1016\/j.drudis.2024.103989","article-title":"Current status of drugs targeting PDGF\/PDGFR","volume":"29","author":"Ai","year":"2024","journal-title":"Drug Discov. 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