Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin

The study demonstrated that Tcf3 and Lef1 played crucial roles in regulating the differentiation of multipotent stem cells in the skin. Tcf3 acted independently of its β-catenin interacting domain to suppress epidermal differentiation and promote features of the follicle outer root sheath and multipotent stem cells, relying on its DNA binding and Groucho repressor-binding domains. In contrast, Lef1 required Wnt signaling and stabilized β-catenin to express hair-specific keratin genes and control hair differentiation. When lacking its β-catenin interacting domain, Lef1 (ΔNLef1) did not mimic Tcf3's effects but instead suppressed hair differentiation and promoted sebocyte differentiation. These findings highlighted the significant role of Tcf3/Lef complexes in determining cell fate lineages in skin stem cells.