TY - JOUR TI - The murine intestinal stem cells are highly sensitive to the modulation of the T3/TRα1-dependent pathway AU - Godart, Matthias AU - Frau, Carla AU - Farhat, Diana AU - Giolito, Maria Virginia AU - Jamard, Catherine AU - Nevé, Clementine Le AU - Freund, Jean-Noel AU - Penalva, Luiz O. AU - Sirakov, Maria AU - Plateroti, Michelina T2 - Development AB - Skip to Next Section The thyroid hormone T3 and its nuclear receptor TRα1 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 Dio1 and the transporter Mct10, accompanied by a complex response of stem cell- and progenitor-enriched genes. Interestingly, specific TRα1 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 i) the number of the stem cells, ii) the expression of their specific markers and iii) the commitment of progenitors into lineage-specific differentiation. In conclusion, T3 treatment or TRα1 modulation has a rapid and strong effect on intestinal stem cells, broadening our perspectives in the study of T3/TRα1-dependent signaling in these cells. DA - 2021/01/01/ PY - 2021 DO - 10.1242/dev.194357 DP - dev.biologists.org J2 - Development LA - en SN - 0950-1991, 1477-9129 UR - https://dev.biologists.org/content/early/2021/03/19/dev.194357 Y2 - 2021/03/25/15:58:28 ER -