Abstract
Stem cells are critical for the homeostasis of adult tissues. Thyroid hormone (TH), whose intracellular concentration is increased by type 2 deiodinase (D2), is involved in many functions, but its role in quiescence is unknown. Here we show that D2 marks quiescent stem cells in muscle and skin. Genetic D2-depletion in quiescent muscle stem cells triggers their transition from G0 to a GAlert–like state. This increases the proliferative potential of the stem cells, but impairs their self-renewal capacity, leading to depletion of the stem cell pool and regenerative failure over time. Mechanistically, TH sustains Notch signaling, and active Notch overexpression partially rescues D2-depletion. Transient pharmacological inhibition of D2 accelerates muscle regeneration and skin wound healing by promoting stem cell expansion. In conclusion, we show that D2 is a critical metabolic enzyme in maintaining stem cell quiescence and in regulating self-renewal.
Authors
Maria Angela De Stefano, Raffaele Ambrosio, Cristina Luongo, Tommaso Porcelli, Daniela Di Girolamo, Caterina Miro, Monica Dentice, Caterina Missero, Domenico Salvatore
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ISSN: 0021-9738 (print), 1558-8238 (online)