Innovative Regenerative Medicine, Graduate School of Medicine, Kansai Medical University, Hirakata city, Osaka, Japan.
Osaka College of High-Technology, Osaka City, Osaka, Japan.
PLoS One. 2024 May 14;19(5):e0303260. doi: 10.1371/journal.pone.0303260. eCollection 2024.
The nail matrix containing stem cell populations produces nails and may contribute to fingertip regeneration. Nails are important tissues that maintain the functions of the hand and foot for handling objects and locomotion. Tumor chemotherapy impairs nail growth and, in many cases, loses them, although not permanently. In this report, we have achieved the successful differentiation of nail stem (NS)-like cells from human-induced pluripotent stem cells (iPSCs) via digit organoids by stepwise stimulation, tracing the molecular processes involved in limb development. Comprehensive mRNA sequencing analysis revealed that the digit organoid global gene expression profile fits human finger development. The NS-like cells expressed Lgr6 mRNA and protein and produced type-I keratin, KRT17, and type-II keratin, KRT81, which are abundant in nails. Furthermore, we succeeded in producing functional Lgr6-reporter human iPSCs. The reporter iPSC-derived Lgr6-positive cells also produced KRT17 and KRT81 proteins in the percutaneously transplanted region. To the best of our knowledge, this is the first report of NS-like cell differentiation from human iPSCs. Our differentiation method and reporter construct enable the discovery of drugs for nail repair and possibly fingertip-regenerative therapy.
甲母质包含干细胞群体,产生指甲并可能有助于指尖再生。指甲是维持手和脚功能的重要组织,用于处理物体和运动。肿瘤化疗会损害指甲生长,并在许多情况下导致指甲丢失,尽管不是永久性的。在本报告中,我们通过逐步刺激指状类器官成功地从人诱导多能干细胞(iPSC)中分化出指甲干(NS)样细胞,追踪了涉及肢体发育的分子过程。全面的 mRNA 测序分析表明,类器官的全局基因表达谱与人类手指发育相吻合。NS 样细胞表达 Lgr6 mRNA 和蛋白,并产生大量存在于指甲中的 I 型角蛋白 KRT17 和 II 型角蛋白 KRT81。此外,我们成功地产生了功能性 Lgr6 报告基因 iPSC。在经皮移植区域,报告基因 iPSC 衍生的 Lgr6 阳性细胞也产生了 KRT17 和 KRT81 蛋白。据我们所知,这是首例从人 iPSC 中分化出 NS 样细胞的报告。我们的分化方法和报告基因构建体使发现指甲修复和指尖再生治疗药物成为可能。
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