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Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [scRNA-seq]

ABSTRACT: Using single-cell RNA-sequencing (scRNA-seq), we characterize diverse immune cell infiltrates that remodel the tissue microenvironment following senescence activation in female Znrf3 cKO mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE201126 | GEO | 2023/04/03

REPOSITORIES: GEO

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Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [bulk RNA-seq]

Project description:Using the adrenal gland as a model, we investigated the interplay between genetic Znrf3 inactivation and the aging microenvironment. We hypothesized that SF1-Cre-driven Znrf3 cKO mice would progress from adrenal hyperplasia to carcinoma with age. Unexpectedly, after an initial phase of hyperplasia, we found that Znrf3 cKO adrenals steadily regress over time. We demonstrate this phenotypic switch from hyperplasia to regression is driven by activation of cellular senescence and a subsequent senescence-associated secretory phenotype (SASP).

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Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-03 | GSE201127 | GEO

Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner

Project description:Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner

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Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [scRNA-seq]

Project description:Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [scRNA-seq]

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Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [bulk RNA-seq]

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Gonadal sex reversal at single-cell resolution in Znrf3-deficient mice

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Kinetic comparative analysis of gene expression in whole adrenal glands from Znrf3 cKO and control mice

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Genome wide analysis of Adrenal Gland tissue from Gata6 conditional knockout versus Control Adrenal tissue

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

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Genome wide analysis of Adrenal Gland tissue from Gata6 conditional knockout versus Control Adrenal tissue

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