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GSE108595
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The R47H variant of TREM2 is associated with higher risk of Alzheimer's disease. We generated mice expressing the common variant or R47H variant of human TREM2
Publication Title
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6NKp46 DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear.
Publication Title
IL-15 sustains IL-7R-independent ILC2 and ILC3 development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection.
Publication Title
SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection.
Publication Title
SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 89 Downloadable Samples
NextSeq 500
Description
Alzheimer''s disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, the roles of immune cell subsets in AD onset and progression are poorly understood. By transcriptional single cell sorting, we comprehensively map all immune populations in wild type and AD–transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify the markers, spatial-location, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices showed DAM with intracellular/phagocytic Aß particles. Single cell analysis of DAM in Tg-AD and Trem2-/- Tg-AD revealed that the DAM program is activated in a two-step process. Activation is initiated in a Trem2 independent manner which involves down-regulation of microglia checkpoints, followed by activation of a Trem2-dependent program. These data identify a unique microglia-type, which may have important implications for future treatment of AD and other neurodegenerative diseases. Overall design: Transcriptional profiling of single cells from immune populations of mouse models of neurodegenerative diseases with matched controls, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500
Publication Title
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-ß (Aß) peptide. ApoE influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aß in the brain. In addition to influencing Aß metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1?E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aß morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology. Overall design: Assessed the cortical gene expression of 6-month old APPPS1-21;ApoE-/- (n=7) and APPPS1-21 mice (n=6).
Publication Title
ApoE facilitates the microglial response to amyloid plaque pathology.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500
Description
The most common form of senile dementia, Alzheimer’s disease (AD), is characterized by Aß plaques and neurofibrillary tangles in the CNS. AD genetic studies have identified high-risk hypomorphic variants in TREM2, a myeloid cell surface receptor that enables concerted microglial responses to Aß plaques and neuronal cell death, including proliferation, survival, clustering and phagocytosis. How TREM2 promotes these responses is not known. Here, we demonstrate that TREM2 drives mTOR signaling, which maintains high ATP levels, supports biosynthetic pathways and suppresses AMPK phosphorylation and autophagy. In vitro, TREM2-deficient macrophages undergo dramatically increased autophagy and die in response to growth factor limitation or ER stress. Excessive autophagy is also evident in microglia from Trem2-/- 5XFAD mice and in post-mortem specimens from AD patients carrying TREM2 risk variants. Metabolic derailment, autophagy and cell death can be circumvented by engaging alternative energy production pathways. Thus, restoring microglial energetic and anabolic levels may be a future therapeutic avenue for TREM2-associated neurological disease. Overall design: Bone marrow-derived macrophages (BMDMs) from WT and Trem2–/– mice were cultured in either 0.5% or 10% LCCM overnight in complete RPMI. Some samples cells were stimulated with 10 ng/ml LPS for 4 hours.
Publication Title
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- NextSeq 500
Description
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of T regulatory (Treg) cells and make autoantibodies, but seldom develop autoimmunity. We show that similarly, Dock8-/- mice have decreased numbers and impaired in vitrofunction of Treg cells, but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Treg cells develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite normal percentage and in vitro function of Treg cells, suggesting that deficient T effector cell function might protect DOCK8 deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2 driven STAT5 phosphorylation in Treg cells. DOCK8 localizes within the lamellar actin ring of the Treg cell immune synapse (IS). Dock8-/- Treg cells have abnormal TCR-driven actin dynamics, decreased adhesiveness, altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the co-stimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Treg cells. Overall design: CD4+CD25+CD39+YFP+ and CD4+CD25+CD39+YFP- Treg cells were isolated from the spleen and lymph nodes of Foxp3YFP-Cre/+/Dock8flox/flox mice. Treg cells were then cultured overnight in complete media alone or in the presence of media + anti-CD3+CD28 beads (1 bead per cell). After 16 hours, cells were harvested and the RNA was isolated. For unstimulated samples, there were 4 independent YFP- samples and 6 independent YFP+ samples. For bead stimulated samples, there were 3 independent YFP- samples and 2 YFP+ samples.
Publication Title
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bone marrow mesenchymal stem cells (MSC) were adipogenically differentiated followed by dedifferentiation. We are interested to know the new fat markers, adipogenic signaling pathways and dedifferentiation signaling pathways.Furthermore we are also intrested to know that how differentiated cells convert into dedifferentiated progenitor cells. To address these questions, MSC were adipogenically differentiated, followed by dedifferentiation. Finally these dedifferentiated cells were used for adipogenesis, osteogenesis and chondrogenesis. Histology, FACS, qPCR and GeneChip analyses of undifferentiated, adipogenically differentiated and dedifferentiated cells were performed. Regarding the conversion of adipogenically differentiated cells into dedifferentiated cells, gene profiling and bioinformatics demonstrated that upregulation (DHCR24, G0S2, MAP2K6, SESN3) and downregulation (DST, KAT2, MLL5, RB1, SMAD3, ZAK) of distinct genes play a curcial role in cell cycle to drive the adipogenically differentiated cells towards an arrested state to narrow down the lineage potency. However, the upregulation (CCND1, CHEK, HGF, HMGA2, SMAD3) and downregulation (CCPG1, RASSF4, RGS2) of these cell cycle genes motivates dedifferentiation of adipogenically differentiated cells to reverse the arrested state. We also found new fat markers along with signaling pathways for adipogenically differentiated and dedifferentiated cells, and also observed the influencing role of proliferation associated genes in cell cycle arrest and progression.
Publication Title
Transdifferentiation of adipogenically differentiated cells into osteogenically or chondrogenically differentiated cells: phenotype switching via dedifferentiation.
Sample Metadata Fields
Specimen part
View Samples