Murine intestinal stem cells are highly sensitive to modulation of the T3/TRα1-dependent pathway

The thyroid hormone T3 and its nuclear receptor TR alpha 1 control gut development and homeostasis through the modulation of intestinal crypt cell proliferation. Despite increasing data, in-depth analysis on their specific action on intestinal stem cells is lacking. By using ex vivo 3D organoid cultures and molecular approaches, we observed early responses to T3 involving the T3-metabolizing enzyme Diol and the transporter Mct10, accompanied by a complex response of stem cell- and progenitor-enriched genes. Interestingly, specific TR alpha 1 loss-of-function (inducible or constitutive) was responsible for low ex vivo organoid development and impaired stem cell activity. T3 treatment of animals in vivo not only confirmed the positive action of this hormone on crypt cell proliferation but also demonstrated its key action in modulating the number of stem cells, the expression of their specific markers and the commitment of progenitors into lineage-specific differentiation. In conclusion, T3 treatment or TR alpha 1 modulation has a rapid and strong effect on intestinal stem cells, broadening our perspectives in the study of T3/TR alpha 1-dependent signaling in these cells.

Automated summary

The thyroid hormone T3 and its nuclear receptor TRα1 have a rapid and strong effect on intestinal stem cells, modulating the number of stem cells, the expression of their specific markers, and the commitment of progenitors into lineage-specific differentiation, which broadens perspectives in T3/TRα1-dependent signaling research in these cells.