Asset Details
Do you wish to reserve the book?
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
Do you wish to request the book?
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
2023
Overview
The thyroid functions as an apex endocrine organ that controls growth, differentiation and metabolism
1
, and thyroid diseases comprise the most common endocrine disorders
2
. Nevertheless, high-resolution views of the cellular composition and signals that govern the thyroid have been lacking
3
,
4
. Here, we show that Notch signalling controls homeostasis and thermoregulation in adult mammals through a mitochondria-based mechanism in a subset of thyrocytes. We discover two thyrocyte subtypes in mouse and human thyroids, identified in single-cell analyses by different levels of metabolic activity and Notch signalling. Therapeutic antibody blockade of Notch in adult mice inhibits a thyrocyte-specific transcriptional program and induces thyrocyte defects due to decreased mitochondrial activity and ROS production. Thus, disrupting Notch signalling in adult mice causes hypothyroidism, characterized by reduced levels of circulating thyroid hormone and dysregulation of whole-body thermoregulation. Inducible genetic deletion of Notch1 and 2 in thyrocytes phenocopies this antibody-induced hypothyroidism, establishing a direct role for Notch in adult murine thyrocytes. We confirm that hypothyroidism is enriched in children with Alagille syndrome, a genetic disorder marked by Notch mutations, suggesting that these findings translate to humans.
Mosteiro et al. show that inhibition of Notch, a signaling pathway frequently associated with cell-fate decisions during development, impairs thyrocyte homeostasis in an active subset of thyrocytes in adult mice through mitochondrial dysfunction and decreased ROS, thereby causing hypothyroidism.
