Lmo3-expressing peri-isthmus progenitor cells sustain renewal and repair of the mammalian intestinal telocyte niche

Intestinal telocytes that reside immediately beneath the intestinal epithelium exert niche-supporting roles for intestinal stem cells and their progenies. They are heterogeneous cells compartmentalized along the crypt-villus axis, but the mechanisms governing the maintenance of this telocyte population remain unclear. Here, we identify a distinct population of subepithelial mesenchymal cells in the developing mouse embryo, marked by LIM Domain Only 3 (Lmo3), as the cellular origin of post-natal intestinal telocytes. The Lmo3⁺ cells emerge prior to villus formation at embryonic day 13.5, and after birth, they progressively acquire a spatial confinement to the intestinal isthmus region, where they persist as long-lived, slow-cycling cells, supplying both peri-villus and peri-crypt telocytes. Further, we show that Lmo3⁺ cells respond rapidly to tissue damage, becoming activated to promote repair of the telocyte niche. Therefore, a quiescent and damage-responsive progenitor cell population marked by Lmo3 maintains the intestinal telocyte niche.