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Updated: Nov 11, 2025
Induced Differentiation of M Cell-like Cells in Human Stem Cell-derived Ileal Enteroid Monolayers
Published on: July 26, 2019
Murine intestinal stem cells are highly sensitive to modulation of the T3/TRα1-dependent pathway
Matthias Godart1, Carla Frau1, Diana Farhat1
1Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Université de Lyon, Université Lyon 1, Centre Léon Bérard, Département de la recherche, 69000 Lyon, France.
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.
Insights
Thyroid hormone T3 and its nuclear receptor TRα1 are crucial for intestinal stem cell function and gut homeostasis. Their modulation rapidly impacts stem cell activity, proliferation, and differentiation.
Area of Science:
- Gastroenterology
- Endocrinology
- Developmental Biology
Background:
- Thyroid hormone (T3) and its nuclear receptor TRα1 regulate gut development and homeostasis.
- The precise role of T3/TRα1 signaling in intestinal stem cells (ISCs) remains incompletely understood.
Purpose of the Study:
- To investigate the specific actions of T3 and TRα1 on intestinal stem cells and their function.
- To elucidate the molecular mechanisms underlying T3/TRα1-mediated effects on ISC proliferation and differentiation.
Main Methods:
- Utilized ex vivo 3D organoid cultures derived from the intestine.
- Employed molecular approaches to analyze gene expression and cellular responses.
- Conducted in vivo studies using animal models with specific TRα1 loss-of-function.
Main Results:
- Early T3 response involves the T3-metabolizing enzyme Dio1 and transporter Mct10, affecting ISC-enriched genes.
- TRα1 loss-of-function impaired ex vivo organoid development and ISC activity.
- In vivo T3 treatment enhanced crypt cell proliferation, modulated ISC numbers, and influenced progenitor differentiation.
Conclusions:
- T3 and TRα1 signaling exert rapid and significant effects on intestinal stem cells.
- Modulation of T3/TRα1 signaling offers potential therapeutic avenues for gut-related disorders.
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