Niche cells regulate primordial germ cell quiescence in response to basement membrane signaling

Abstract

Stem cell quiescence, proliferation and differentiation are controlled by interactions with niche cells and a specialized extracellular matrix called the basement membrane (BM). Direct interactions with adjacent BM are known to regulate stem cell quiescence; however, it is less clear how niche BM relays signals to stem cells that it does not contact. Here, we examine how niche BM regulates C. elegans primordial germ cells (PGCs), which remain quiescent during embryogenesis. Depleting the BM protein laminin causes embryonic PGCs to proliferate, indicating that laminin functions to maintain PGC quiescence. How laminin signals to the PGCs remains unclear, as somatic niche cells enwrap PGCs and physically exclude them from contacting the BM. Here, we show that, following laminin depletion, gonadal niche cells relay proliferation-inducing signals from the gonadal BM to PGCs via integrin receptors. Mutations disrupting the BM proteoglycan perlecan block PGC proliferation when laminin is depleted, suggesting that laminin functions to inhibit a proliferation-inducing signal originating from perlecan. Our results reveal how BM signals can regulate stem cell quiescence indirectly, by activating niche cell integrin receptors.