The Thyroid Hormone Nuclear Receptor TR1 Plays An Essential Role In Intestinal Epithelium Stem Cell Physiopathology

Giolito, Maria Virginia;et.al.
(2021) 21e Journée Scientifique de la Ligue Contre le cancer. — Location: Illkirch, France (9.November.2021)

Files

No attached file found for this publication.

Details

Authors
Abstract
The thyroid hormone T3 and its nuclear receptor TR1 control gut development and homeostasis through the modulation of intestinal crypt cell proliferation (rev. in Skah et al, Dev. Biol_2017; Sirakov et al, CMLS_2014). We have recently performed an in depth analysis on their specific action on intestinal stem cells (SC) (Godart et al, Develop._2021). Indeed, 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 SC- and progenitor-enriched genes. Interestingly, specific TR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 i) the number of the stem cells, ii) the expression of their specific markers and iii) the commitment of progenitors into lineage-specific differentiation. Our current work aims to: -Analyze the impact of T3/TR1 on intestinal cancer SCs (CSC) in animals in vivo (Lgr5-EGFP-CreERT2/TR1-LOF/Apcf/+ mice), in spheroids from Caco2 colon adenocarcinoma cell line (Giolito et al, JoVE_2021) and human organoids from patients CRCs (Frau et al, Cancer Research_2021); -Better define the TR1-expressing cells by using the TR1-GFP mice, where the GFP recapitulate the expression of the TR1 protein (Wallis et al, Mol. Endocrinol._2014), in a WT or an Apcf/+ background. Keywords: Intestinal stem cells; Thyroid hormone nuclear receptor; Tumor spheroids; Tumor organoids
Affiliations
  • Université de Strasbourg, Inserm, IRFAC/UMR-S1113, FMTS. 3, Avenue Molière, 67200 Strasbourg, France

Citations

  • APA
  • Chicago
  • FWB

Giolito, M. V., & et al. (2021). The Thyroid Hormone Nuclear Receptor TR1 Plays An Essential Role In Intestinal Epithelium Stem Cell Physiopathology. 21e Journée Scientifique de la Ligue Contre le cancer., Illkirch, France. https://hdl.handle.net/2078.5/267780