Single-cell analysis reveals that the hormone T3 affects colon epithelial differentiation and induces a mixed progenitor-like cell population.

During amphibian metamorphosis, a postembryonic developmental process, the thyroid hormone T3 induces multiple responses across organs and tissues, including intestinal remodeling. Indeed, the intestine reaches full maturity under the influence of this hormone, which, by acting through the nuclear receptors TRs, also induces the neogenesis of epithelial stem cells. A symmetric function of T3/TRα1 has been established in the developing mammalian intestine, as well as in the control of epithelial homeostasis and stem cell biology. While most studies have focused on the mammalian small intestine, very few have investigated T3 function in the colon, and none have done so at the single-cell level. We investigated here how T3 affects the physiological renewal of colon epithelium using a single-cell (sc) RNA-seq approach. Our results reveal a T3-dependent alteration of differentiation trajectories and immunolabeling experiments show an accumulation of committed goblet progenitors at the bottom of colonic crypts. Altogether, these results describe, for the first time, the action of T3 on distinct colon epithelial cell populations in the mouse. In addition, they provide further evidence on the mechanisms underlying T3’s role in controlling cell fate during physiological regeneration.