APA
Contreras Jurado, Silvia Constanza & Lorz, Corina & García Serrano, Laura & Paramio, Jesus M. & Aranda, Ana .Thyroid hormone signaling controls hair follicle stem cell function.
ISO 690
Contreras Jurado, Silvia Constanza & Lorz, Corina & García Serrano, Laura & Paramio, Jesus M. & Aranda, Ana. Thyroid hormone signaling controls hair follicle stem cell function.
https://hdl.handle.net/20.500.12080/26180
Resumen:
Observations in thyroid patients and experimental animals show that the skin is
an important target for the thyroid hormones. We previously showed that deletion in mice of
the thyroid hormone nuclear receptors TR¿1 and TR¿ (the main thyroid hormone¿binding
isoforms) results in impaired epidermal proliferation, hair growth, and wound healing. Stem
cells located at the bulges of the hair follicles are responsible for hair cycling and contribute
to the regeneration of the new epidermis after wounding. Therefore a reduction in the num ber or function of the bulge stem cells could be responsible for this phenotype. Bulge cells
show increased levels of epigenetic repressive marks, can retain bromodeoxyuridine labeling
for a long time, and have colony-forming efficiency (CFE) in vitro. Here we demonstrate that
mice lacking TRs do not have a decrease of the bulge stem cell population. Instead, they
show an increase of label-retaining cells (LRCs) in the bulges and enhanced CFE in vitro. Re duced activation of stem cells leading to their accumulation in the bulges is indicated by a
strongly reduced response to mobilization by 12-O-tetradecanolyphorbol-13-acetate. Al tered function of the bulge stem cells is associated with aberrant activation of Smad signal ing, leading to reduced nuclear accumulation of ¿-catenin, which is crucial for stem cell prolif eration and mobilization. LRCs of TR-deficient mice also show increased levels of epigenetic
repressive marks. We conclude that thyroid hormone signaling is an important determinant
of the mobilization of stem cells out of their niche in the hair bulge. These findings correlate
with skin defects observed in mice and alterations found in human thyroid disorders.