{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:36:21Z","timestamp":1785418581038,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"publisher","award":["24K11710"],"award-info":[{"award-number":["24K11710"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24K11710"],"award-info":[{"award-number":["24K11710"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Several protocols have been reported for inducing parathyroid differentiation from human pluripotent stem cells in vitro. However, the efficiency of terminal differentiation into mature parathyroid cells remains limited. In this study, we performed comparative transcriptomic analyses of parathyroid lineage-induced human induced pluripotent stem (iPS) cells to clarify their developmental stage identity. Comparative analyses with adult parathyroid adenoma, used as a surrogate reference for mature parathyroid cells, and thymuses revealed that the differentiated cells exhibited gene expression patterns consistent with early-stage parathyroid and thymus development, including TBX1, which is required for fate determination of the parathyroid\u2013thymic primordium. On the other hand, the expression of mature parathyroid marker genes, such as PTH, GCM2, and the calcium-sensing receptor (CaSR), remained markedly lower than that in parathyroid adenoma. Under the differentiation conditions and durations examined, application of modified differentiation protocols did not significantly enhance the expression of mature parathyroid markers, although pharyngeal pouch developmental gene expression was maintained. Our findings indicate that current in vitro differentiation systems effectively induce the parathyroid\u2013thymic primordium stage, while a developmental bottleneck at the transition from the primordium toward parathyroid lineage commitment remains.<\/jats:p>","DOI":"10.3390\/cells15141252","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Transcriptomic Analysis of Human iPSC-Derived Parathyroid Lineage Cells Reveals Limited Maturation Beyond the Parathyroid\u2013Thymic Primordium"],"prefix":"10.3390","volume":"15","author":[{"given":"Chie","family":"Kise","sequence":"first","affiliation":[{"name":"Department of Geriatric Dentistry, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"},{"name":"Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusuke","family":"Nakatsuka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"},{"name":"Department of iPS Stem Cell Regenerative Medicine, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyo","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-1898","authenticated-orcid":false,"given":"Yuka","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Hitomi","sequence":"additional","affiliation":[{"name":"Department of iPS Stem Cell Regenerative Medicine, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2386-0060","authenticated-orcid":false,"given":"Tadashige","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Hirakata 573-1121, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1089\/scd.2023.0130","article-title":"The induction of parathyroid cell differentiation from human induced pluripotent stem cells promoted via TGF-\u03b1\/EGFR signaling","volume":"32","author":"Nakatsuka","year":"2023","journal-title":"Stem Cells Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13634","DOI":"10.1111\/cpr.13634","article-title":"Directed differentiation of human embryonic stem cells into parathyroid cells and establishment of parathyroid organoids","volume":"57","author":"Wang","year":"2024","journal-title":"Cell Prolif."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"bqaa141","DOI":"10.1210\/endocr\/bqaa141","article-title":"Differentiation of PTH-expressing cells from human pluripotent stem 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