The disrupted genetic mechanisms underlying neural abnormalities in Autism Spectrum Disorder remain mostly unknown and speculative. No biological marker nor genetic signature is currently available to assist with early diagnosis.
Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices.
Sex, Specimen part
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Microglia were isolated from the brains of adult male c57BL/6 mice given bone marrow tranplants (BMT) with or without head shield. All mice received PLX5622 for 2 weeks, then placed and normal chow to recoever. Some mice were then challenged with LPS. Cells were isolated by MACS using CD11b magnetic beads.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Mice were given 1000rad whole body irradiation, followed by bone marrow transplant with UBC-GFP bone marrow at 8 weeks of age. Engraftment was allowed to occur for 8 months, then engrafting macrophages and microglia were isolated from whole brains for RNA-Seq.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Subject
View SamplesRole of CTCF in activated B cells. Overall design: Transcriptome profiling of CTCF deficient and proficient activated in vitro B cells.
CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation.
Specimen part, Subject
View SamplesSalp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in immunomodulation in different murine models in which these cells participate. The fate of the CD4 T cells activated in the presence of the immunosuppressor or its long-term effects on these cells are however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished antibody production against specific and unrelated antigens. Transcriptionally, the salivary protein provokes a sharp acute effect that includes known activation factors, such as Il2, Cd44, or Il2ra, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with the immunomodulatory protein does not result in B cell anergy or the generation of myeloid suppressor cells. However, the immunomodulatory protein induces the increased expression of the ectoenzyme, CD73, in regulatory T cells. Our results suggest that the specific regulation of CD73, a known modulator of adenosine levels, by Salp15 results in long-term cross-antigenic immunomodulatory effects. Overall design: Genome-wide changes in gene Expression in mouse CD4 T cells activated with anti-CD3/CD28 in the presence of 25 ug/mL of the tick salivary protein, Salp15 or its inactive control (Salp15deltaP11) were generated by RNAseq.
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.
Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesSox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View Samples