Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. After different conditioning paradigms and bone marrow (BM) or hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that graft-derived macrophages acquire, over time, microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even after prolonged CNS residence, transcriptomes and chromatin accessibility landscapes of engrafted, BM-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, engrafted BM-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. In human HSC transplant recipients, engrafted cells also remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for HSC gene therapies aimed to ameliorate lysosomal storage disorders, microgliopathies or general monogenic immuno-deficiencies. Overall design: overall there are 28 samples, from total of 2 experiments. in each experiment there were at least 3 biological repeats (3 individual mice). Sorting of the CD45.1 and CD45.2 populations were performed from the same animal. Animals were either injected with LPS (2.5 mg/kg) or untreated.
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge.
Specimen part, Cell line, Subject
View SamplesExpression of the yeast Cth2 protein stimulates degradation of mRNAs encoding proteins with Fe-dependent functions in metabolism, in iron storage and in other cellular processes. We demonstrate that in response to Fe deprivation, the Cth2-homologue, Cth1, stimulates specific degradation of mRNAs involved in mitochondrially localized activities that include respiration and amino acid biosynthesis. Furthermore, yeast cells grown under Fe deprivation accumulate mRNAs encoding proteins that function in glucose metabolism. These studies demonstrate a reprogramming of cellular metabolism during Fe-starvation dependent on the coordinated activities of two mRNA binding proteins.
Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency.
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Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages.
No sample metadata fields
View SamplesTissue-resident macrophages comprise heterogeneous populations with unique functions and distinct gene expression signatures. While it has been established that they mostly originate from embryonic progenitors, the signals inducing a characteristic tissue-specific differentiation program remain unknown. Here we identify PPAR as the crucial transcription factor determining perinatal alveolar macrophage (AM) development and identity. Development of the fetal monocyte derived AM precursor was largely abrogated in CD11c-Cre/Ppargfl/fl mice. To reveal the underlying changes in gene expression, we performed microarray analysis of sorted WT and KO AM and pre-AM from 3 different timepoints.
Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages.
No sample metadata fields
View SamplesTissue-resident macrophages comprise heterogeneous populations with unique functions and distinct gene expression signatures. While it has been established that they mostly originate from embryonic progenitors, the signals inducing a characteristic tissue-specific differentiation program remain unknown. Here we identify PPAR as the crucial transcription factor determining perinatal alveolar macrophage (AM) development and identity. Development of the fetal monocyte derived AM precursor was largely abrogated in CD11c-Cre/Ppargfl/fl mice. To reveal the underlying changes in gene expression, we performed microarray analysis of sorted WT and KO AM and pre-AM from 3 different timepoints.
Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages.
No sample metadata fields
View Samplestreatment of mesenteric lymph nodes with soluble lymphotoxin-beta receptor for 0,1,2,3,27 and 35 days
Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes.
No sample metadata fields
View SamplesTwo human acute lymphoblastic leukemia cell lines (Molt-4 and CCRF-CEM) were treated with direct (A-769662) and indirect (AICAR) AMPK activators. Molt-4 and CCRF-CEM cells were obtained from ATCC (CRL-1582 and CCL-119). Control samples were used for the analysis of metabolic differences between cell lines. Therefore the data was analyzed in combination with, metabolomic data, and the genome-scale reconstruction of human metabolism. For experiments cells were grown in serum-free medium containing DMSO (0.67%) at a cell concentration of 5 x 105 cells/mL.
Prediction of intracellular metabolic states from extracellular metabolomic data.
Cell line, Treatment
View SamplesComparison of follicular dendritic cell-enriched versus -depleted splenocytes
Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes.
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The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.
Specimen part, Disease, Disease stage, Cell line
View SamplesWe identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with ChIP-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture (SILAC), we identified directly and indirectly regulated targets of the TEL-AML1 fusion protein.
The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.
Cell line
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