GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue

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Doerner , J , Rodriguez , V M , Ziegler , R , Roehrig , T , Cochran , R S , Goetz , R M , Levin , M D , Pihlajoki , M , Heikinheimo , M & Wilson , D B 2017 , ' GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue ' , Molecular and Cellular Endocrinology , vol. 441 , no. C , pp. 164-175 . https://doi.org/10.1016/j.mce.2016.08.043

Title: GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue
Author: Doerner, Julia; Rodriguez, Verena Martinez; Ziegler, Ricarda; Roehrig, Theresa; Cochran, Rebecca S.; Goetz, Ronni M.; Levin, Mark D.; Pihlajoki, Marjut; Heikinheimo, Markku; Wilson, David B.
Other contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum




Date: 2017-02-05
Language: eng
Number of pages: 12
Belongs to series: Molecular and Cellular Endocrinology
ISSN: 0303-7207
DOI: https://doi.org/10.1016/j.mce.2016.08.043
URI: http://hdl.handle.net/10138/233336
Abstract: As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1(+) progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Glil-creER(T2)) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1(+) cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1(+) progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1(+) progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Foxl2) in response to GDX. These findings support the premise that GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Subject: Adrenal cortex
Gonadectomy
Gonadotropin
Lineage tracing
Orchiectomy
Ovariectomy
INDUCED ADRENOCORTICAL-NEOPLASIA
PERITUBULAR CELLS
LEYDIG-CELLS
STEM-CELLS
MICE
FETAL
DIFFERENTIATION
PROLIFERATION
ACTIVATION
EXPRESSION
3121 General medicine, internal medicine and other clinical medicine
1182 Biochemistry, cell and molecular biology
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