Project description:Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We defined the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and used genetic models to explore the developmental mechanisms yielding to macrophage diversity. We defined populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identified a female-specific subset with low MHC-II expression. In adulthood, monocyte recruitment dominated adrenal gland macrophage maintenance in female mice, while self-proliferation was more important in males. Adrenal gland macrophage sub-tissular distribution followed a sex-dimorphic pattern, with MHC-IIlow macrophages located at the border between the cortex and the medulla. Macrophage sex dimorphism depended on the presence of the cortical Xzone. Forcing X-zone maintenance in males, or its degradation in females, directly impacted the presence of MHC-IIlow macrophages. Adrenal gland macrophage depletion resulted in altered tissue homeostasis, modulated lipid- metabolism and decreased local aldosterone production during stress exposure. Overall, these data explain the heterogeneity of adrenal gland macrophages and point toward sexrestricted distribution and functions of these cells.
Project description:Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We defined the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and used genetic models to explore the developmental mechanisms yielding to macrophage diversity. We defined populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identified a female-specific subset with low MHC-II expression. In adulthood, monocyte recruitment dominated adrenal gland macrophage maintenance in female mice, while self-proliferation was more important in males. Adrenal gland macrophage sub-tissular distribution followed a sex-dimorphic pattern, with MHC-IIlow macrophages located at the border between the cortex and the medulla. Macrophage sex dimorphism depended on the presence of the cortical Xzone. Forcing X-zone maintenance in males, or its degradation in females, directly impacted the presence of MHC-IIlow macrophages. Adrenal gland macrophage depletion resulted in altered tissue homeostasis, modulated lipid- metabolism and decreased local aldosterone production during stress exposure. Overall, these data explain the heterogeneity of adrenal gland macrophages and point toward sexrestricted distribution and functions of these cells.
Project description:Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.
Project description:This study was performed to analyze differentai gene expression profiles in the mouse adrenal gland according to age and sex (in an age-matched fashion)
Project description:This study was performed to identify active enhancers (as defined by H3K27ac enrichment) in the mouse adrenal gland according to age and sex (in an age-matched fashion)
Project description:The libraries contained in this experiment come from adult 8 week adrenal gland tissue from mixed sex littermates in mouse strain C57BL/6J. They are stranded PE76 Illumina GAIIx RNA-Seq libraries from rRNA-depleted Poly-A+ RNA > 200 nucleotides in size. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex with thickened capsule. Cytomegalic changes were evident in the adrenal glands of fetal and adult cKO mice, and chromaffin cells were ectopically located at the periphery of the glands. The secretion of corticosterone in response to exogenous ACTH was blunted in cKO mice. Cells expressing gonadal-like markers, including Gata4, Amhr2, and Tcf21, accumulated in the adrenal capsule and subcapsule of cKO mice, suggesting aberrant adrenocortical progenitor/stem cell differentiation. Gonadectomy triggered the overexpression of sex steroidogenic differentiation markers, such as Lhcgr and Cyp17, in the adrenal glands of male and female cKO mice. Nulliparous female and orchiectomized male cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of nulliparous female Gata6 cKO mice. Our findings offer genetic proof of the longstanding hypothesis that GATA6 regulates the differentiation of steroidogenic progenitors into corticoid-producing cells. 3 replicates from both conditional knockout of Gata6 in the adrenal gland and control adrenal glands from non-knockout mice were compared