Microglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Specimen part, Cell line, Subject
View SamplesMicroglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Sex, Specimen part, Cell line, Subject
View SamplesIn the ovarian follicle, maturation of the oocyte increases in the presence of somatic cells called cumulus cells (CCs). These cells form a direct barrier between the oocyte and external environment. Thanks to bidirectional communication, they have a direct impact on the oocyte, its quality and development potential. Understanding the genetic profile of CCs appears to be important in elucidating the physiology of oocytes. In this work, CCs were subjected to in vitro long-term culture. RNA was collected after 1, 7, 15 and 30 days of culture. Expression microarrays were used for analysis, which allowed to identify groups of genes characteristic for particular cellular processes.
Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging-A Study of New Molecular Markers.
Sex, Specimen part
View SamplesThe proper mammalian oocytes maturation is recognized as reaching MII stage and accumulation of mRNA and proteins in cell cytoplasm following fertilization. The proper course of folliculogenesis and oogenesis is orchestrated with morphogenesis significantly influencing further zygote formation and embryos growth. This study was aimed to determinate new transcriptomic markers of porcine oocytes morphogenesis associated with cell maturation capacity.
"Cell Migration" Is the Ontology Group Differentially Expressed in Porcine Oocytes Before and After In Vitro Maturation: A Microarray Approach.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View SamplesExtraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 g T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View SamplesExtraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 g T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats.
No sample metadata fields
View SamplesEquine lameller tissues were collected to compare normal vs laminitis generated differences in transcriptom level.
Gene expression in the lamellar dermis-epidermis during the developmental phase of carbohydrate overload-induced laminitis in the horse.
No sample metadata fields
View SamplesPURPOSE. To determine global mRNA expression levels in the corneal and conjunctival epithelia and identify transcripts that exhibit preferential tissue expression.
Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays.
No sample metadata fields
View SamplesPurpose: To examine and characterize the expression profile of genes expressed at the neuromuscular junctions (NMJs) of extraocular muscles (EOMs) in comparison to the NMJs of tibialis anterior muscle (TA).
Identification of the neuromuscular junction transcriptome of extraocular muscle by laser capture microdissection.
Specimen part
View Samples