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Article Dans Une Revue Development (Cambridge, England) Année : 2021

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

Matthias Godart
  • Fonction : Auteur
Carla Frau
  • Fonction : Auteur
Diana Farhat
  • Fonction : Auteur
Maria Virginia Giolito
Catherine Jamard
  • Fonction : Auteur
Clementine Le Nevé
  • Fonction : Auteur
Luiz Penalva
  • Fonction : Auteur
Maria Sirakov
  • Fonction : Auteur
Michelina Plateroti

Résumé

ABSTRACT 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 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 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.

Domaines

Cancer

Dates et versions

hal-03791609 , version 1 (29-09-2022)

Identifiants

Citer

Matthias Godart, Carla Frau, Diana Farhat, Maria Virginia Giolito, Catherine Jamard, et al.. Murine intestinal stem cells are highly sensitive to modulation of the T3/TRα1-dependent pathway. Development (Cambridge, England), 2021, 148 (8), ⟨10.1242/dev.194357⟩. ⟨hal-03791609⟩
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