What is it about?
Plastic regeneration of the digit tip is known in mice, and it is known to be organized by the nail matrix and its stem cells. In this report, we have achieved the successful differentiation of nail matrix stem (NS)-like cells from human 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.
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Why is it important?
Our technique first achieved successful differentiation of digit organoids from human iPSCs, whose global gene expression patterns suggested limb, arm, and finger development-related signatures. The molecular marker of the nail stem cells, Lgr6, marked some cells in the organoids. Enrichment and transplantation of them resulted in hard keratin deposition, suggesting their functionalities.
Perspectives
The plastic regeneration abilities of Newts are envious of us because mammalian regeneration has quite limited abilities. However, we focused on the digit tip regeneration ability observed in adult mice. Some research has revealed its mechanisms and the significance of nail stem cells for it. We hope this research will contribute to further research on digit tip and nail regeneration therapies.
Fumiyuki Hattori
Innovative Regenerative Medicine, Graduate School of Medicine, Kansai Medical University, Osaka 573-1010, Japan.
Read the Original
This page is a summary of: Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells, PLOS One, May 2024, PLOS,
DOI: 10.1371/journal.pone.0303260.
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