The murine intestinal stem cells are highly sensitive to the modulation of the T3/TRα1-dependent pathway.
Fiche publication
Date publication
mars 2021
Journal
Development (Cambridge, England)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FREUND Jean-Noël, Dr PLATEROTI Michelina
Tous les auteurs :
Godart M, Frau C, Farhat D, Giolito MV, Jamard C, Le Nevé C, Freund JN, Penalva LO, Sirakov M, Plateroti M
Lien Pubmed
Résumé
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 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 organoid development and impaired stem cell activity. T3-treatment of animals 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.
Mots clés
Intestinal stem cells, Organoids, Thyroid hormone, Thyroid hormone nuclear receptor
Référence
Development. 2021 Mar 23;: