{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vickers RR"],"funding":["NICHD NIH HHS","Texas A&M University College Station","Texas A&M University College Station","National Institute of Child Health and Human Development"],"pagination":["dev202998"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11528151"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["151(19)"],"pubmed_abstract":["Heightened energetic and nutrient demand during lactogenic differentiation of the mammary gland elicits upregulation of various stress responses to support cellular homeostasis. Here, we identify the stimulator of interferon genes (STING) as an immune supporter of the functional development of mouse mammary epithelial cells (MECs). An in vitro model of MEC differentiation revealed that STING is activated in a cGAS-independent manner to produce both type I interferons and proinflammatory cytokines in response to the accumulation of mitochondrial reactive oxygen species. Induction of STING activity was found to be dependent on the breast tumor suppressor gene single-minded 2 (SIM2). Using mouse models of lactation, we discovered that loss of STING activity results in early involution of #3 mammary glands, severely impairing lactational performance. Our data suggest that STING is required for successful functional differentiation of the mammary gland and bestows a differential lactogenic phenotype between #3 mammary glands and the traditionally explored inguinal 4|9 pair. These findings affirm unique development of mammary gland pairs that is essential to consider in future investigations into normal development and breast cancer initiation."],"journal":["Development (Cambridge, England)"],"pubmed_title":["Loss of STING impairs lactogenic differentiation."],"pmcid":["PMC11528151"],"funding_grant_id":["R01 HD102149","1R01-HD102149A1","R01ES0336"],"pubmed_authors":["Wyatt GL","West AP","Porter WW","Vickers RR","VanPortfliet JJ","Sanchez L"],"additional_accession":[]},"is_claimable":false,"name":"Loss of STING impairs lactogenic differentiation.","description":"Heightened energetic and nutrient demand during lactogenic differentiation of the mammary gland elicits upregulation of various stress responses to support cellular homeostasis. Here, we identify the stimulator of interferon genes (STING) as an immune supporter of the functional development of mouse mammary epithelial cells (MECs). An in vitro model of MEC differentiation revealed that STING is activated in a cGAS-independent manner to produce both type I interferons and proinflammatory cytokines in response to the accumulation of mitochondrial reactive oxygen species. Induction of STING activity was found to be dependent on the breast tumor suppressor gene single-minded 2 (SIM2). Using mouse models of lactation, we discovered that loss of STING activity results in early involution of #3 mammary glands, severely impairing lactational performance. Our data suggest that STING is required for successful functional differentiation of the mammary gland and bestows a differential lactogenic phenotype between #3 mammary glands and the traditionally explored inguinal 4|9 pair. These findings affirm unique development of mammary gland pairs that is essential to consider in future investigations into normal development and breast cancer initiation.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-04T01:02:39.615Z","creation":"2025-04-04T01:02:39.615Z"},"accession":"S-EPMC11528151","cross_references":{"pubmed":["39399905"],"doi":["10.1242/dev.202998"]}}