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Seladelpar was recently approved for the secondary treatment of primary biliary cholangitis (PBC). Despite its beneficial effects for liver diseases, the target cells of seladelpar on a single\u2010cell level remain unknown. This study is aimed at investigating the effect of seladelpar on single liver cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      CD\u20101 mice were gavaged with vehicle or seladelpar (10\u2009mg\/kg body weight), and the liver was harvested 6\u2009h later. Single\u2010nuclei RNA sequencing (snRNA\u2010seq) analysis showed the engagement of PPARD target genes primarily in hepatocytes and cholangiocytes by seladelpar. The top two upregulated genes,\n                      <jats:italic>Ehhadh<\/jats:italic>\n                      and\n                      <jats:italic>Cyp4a14<\/jats:italic>\n                      , are related to fatty acid metabolism and were increased in hepatocytes, cholangiocytes, and Kupffer cells.\n                      <jats:italic>Abcb4<\/jats:italic>\n                      , an important canalicular transporter with hepatoprotective effects, was significantly upregulated in hepatocytes. We confirmed upregulated\n                      <jats:italic>Abcb4<\/jats:italic>\n                      gene expression in seladelpar\u2010treated primary mouse hepatocytes isolated from C57BL\/6 mice. We further incubated nonparenchymal liver cells with seladelpar. Although there was a significant increase in the PPARD\u2010responsive genes\n                      <jats:italic>Pdk4<\/jats:italic>\n                      and\n                      <jats:italic>Angptl4<\/jats:italic>\n                      in cholangiocytes, Kupffer cells, and hepatic stellate cells, seladelpar did not exert specific liver\u2010protective effects in these cell types.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The selective PPARD agonist seladelpar induced PPARD\u2010responsive genes primarily in hepatocytes and cholangiocytes. Seladelpar upregulated\n                      <jats:italic>Abcb4<\/jats:italic>\n                      in hepatocytes, which might contribute to its beneficial effects in cholestatic liver disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ppar\/2935230","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T14:49:37Z","timestamp":1761230977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Nuclei RNA Sequencing Shows the Engagement of PPAR\u2010Delta Target Genes Primarily in Hepatocytes and Cholangiocytes by the Selective PPAR\u2010Delta Agonist Seladelpar"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6958-1366","authenticated-orcid":false,"given":"Tomoo","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-9778","authenticated-orcid":false,"given":"David","family":"Sch\u00f6ler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Yukawa-Muto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Kouno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-8106","authenticated-orcid":false,"given":"Aenne","family":"Harberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6306-4621","authenticated-orcid":false,"given":"Sadatsugu","family":"Sakane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linton","family":"Freund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2604-1340","authenticated-orcid":false,"given":"Cynthia 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