Stem cells (SCs) offer significant potential in regenerative medicine. Accordingly, understanding the signaling mechanisms controlling their differentiation is of fundamental and practical importance. Ion channels, which exert significant dynamic control over the plasma membrane voltage and intracellular biochemical environment, offer novel insights to the differentiation process. Previously, we evaluated the contribution of Ca2+-activated potassium (KCa) channels to the different stages of mesenchymal SC differentiation along distinct lineages. Here, we discuss the role that Ca2+-permeant and mechanosensitive ion channels play in the physically induced differentiation response of various types of adult SCs. The main focus is on Piezo1 and Piezo2 proteins and transient receptor potential vanilloid 4 (TrpV4) channels. In addition, the mechanosensitivity of KCa channels is considered. We conclude that Piezo and TrpV4 ion channels have significant involvement in adult SC differentiation and could potentially facilitate novel tissue engineering approaches and therapies.
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