A Transcriptomic Analysis of Human iPSC-Derived Parathyroid Lineage Cells Reveals Limited Maturation Beyond the...

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-thymic 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-thymic primordium stage, while a developmental bottleneck at the transition from the primordium toward parathyroid lineage commitment remains.