{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:00:19Z","timestamp":1790776819600,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>Porcine induced pluripotent stem cells (piPSCs) generated via standard reprogramming factors typically remain dependent on exogenous transgene expression to maintain pluripotency and exhibit limited differentiation potential. Improving these limitations is essential for both regenerative medicine and agricultural biotechnology. To enhance the quality of piPSCs, we introduced an episomal plasmid encoding TBX3 in addition to the standard reprogramming factors with transgene\u2010free piPSC lines established via WNT pathway inhibition. Furthermore, we developed optimized differentiation protocols to efficiently generate smooth muscle cells (SMCs), endothelial cells (ECs), hepatocyte\u2010like cells (HLCs), and cardiomyocytes from piPSCs. TBX3\u2010reprogrammed piPSCs (TBX3\u2010piPSC) expressed both SSEA\u20101 and SSEA\u20104 surface markers, in contrast to standard piPSCs, which expressed only SSEA\u20101. TBX3\u2010piPSC rapidly silenced exogenous reprogramming factors and formed teratomas containing well\u2010differentiated tissues from all three germ layers. In contrast, standard piPSCs formed poorly differentiated teratomas composed mainly of mesenchymal and neuroectodermal tissues, consistent with previous reports of transgene\u2010dependent piPSCs. TBX3\u2010piPSC also formed embryoid bodies that demonstrated broader differentiation capacity. Under directed differentiation conditions, TBX3\u2010piPSC efficiently gave rise to SMCs, ECs, HLCs, and beating cardiomyocytes. Thus, we conclude that the addition of TBX3 as a reprogramming factor promotes the generation of transgene\u2010free piPSCs with enhanced differentiation potential. These findings provide a significant advancement in porcine stem cell biology and expand the potential applications of piPSCs.<\/jats:p>","DOI":"10.1111\/febs.70733","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:29:16Z","timestamp":1790774956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improving the differentiation capability of porcine induced pluripotent stem cells by using the additional reprogramming factor\n                    <scp>TBX3<\/scp>"],"prefix":"10.1111","author":[{"given":"Yu\u2010Jing","family":"Liao","sequence":"first","affiliation":[{"name":"Genetics and Physiology Division Taiwan Livestock Research Institute, Ministry of Agriculture  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenn\u2010Rong","family":"Yang","sequence":"additional","affiliation":[{"name":"Genetics and Physiology Division Taiwan Livestock Research Institute, Ministry of Agriculture  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao\u2010Yun","family":"Kuo","sequence":"additional","affiliation":[{"name":"Genetics and Physiology Division Taiwan Livestock Research Institute, Ministry of Agriculture  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Shiou","family":"Chen","sequence":"additional","affiliation":[{"name":"Genetics and Physiology Division Taiwan Livestock Research Institute, Ministry of Agriculture  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ching","family":"Lin","sequence":"additional","affiliation":[{"name":"Genetics and Physiology Division Taiwan Livestock Research Institute, Ministry of Agriculture  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikesh","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, Bond Life Sciences Center University of Missouri  Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology and Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine University of Missouri  Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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