Mechanical Instability of Adherens Junctions Overrides Intrinsic Quiescence of Hair Follicle Stem Cells

Vinculin, a mechano-transducer associated with both adherens junctions (AJ) and focal adhesions (FA) plays a central role in force transmission through these cell-cell and cell-substratum contacts. Here we describe the conditional knock out (KO) of vinculin in the murine skin. Remarkably, we find that the loss of vinculin function results in the loss of bulge stem cell (BuSC) quiescence. We demonstrate that vinculin KO cells are impaired in force generation resulting in mechanically weak AJs. Mechanistically, we show that vinculin functions by keeping alpha catenin in a stretched conformation, which in turn regulates the retention of YAP1, yet another potent mechano-transducer and regulator of cell proliferation, to the junctions. Conditional KO of alpha catenin specifically in the BuSCs further corroborates the importance of stable AJs in the maintenance of quiescence and stemness. Altogether, our data for the first time, provides definitive mechanistic insights into the hitherto unexplored regulatory link between the mechanical stability of cell-junctions and the maintenance of SC quiescence.