RNA sequencing of tissue resident macrophages, progenitors and tumor cells from murine head and neck tumors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139935 | GEO | 2019/11/06
REPOSITORIES: GEO
Similar Datasets
Project description:Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. In this study, we performed gene expression profiling to examine how the transcriptional signatures compared between TSLP-elcited GMP-like cells and naïve bone marrow-resident GMPs. Splenic TSLP-elicited GMP-like cells (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, CD34+ c-kit+) were sort-purified from the spleen of C57BL/6 mice on day 5 post-TSLP-cDNA treatment. BM-resident GMPs (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, Sca1- c-kit+ CD34+ CD16/32+) were sort-purified from mice that received a control-cDNA injection.
2014-03-28 | E-GEOD-52485 | biostudies-arrayexpress
Project description:In vivo pathways of natural retinoid metabolism and elimination have not been well characterized in primary myeloid cells, even though retinoids and retinoid receptors have been strongly implicated in regulating myeloid maturation. Using a UAS-GFP reporter transgene, and retrovirally expressed Gal4-RARA in primary mouse bone marrow cells, we identified two distinct enzymatic pathways utilized by mouse myeloid cells ex vivo to synthesize RARA ligands from free vitamin A metabolites (retinyl acetate, retinol, and retinal). Bulk Kit+ bone marrow progenitor cells utilize diethylaminobenzaldehyde (DEAB)-sensitive enzymes, whereas bone marrow-derived macrophages use DEAB-insensitive enzymes to synthesize natural RARA-activating retinoids (all-trans retinoic acid). Bone marrow-derived macrophages do not express the DEAB-sensitive enzymes Aldh1a1, Aldh1a2, or Aldh1a3, but instead express Aldh3b1, which we found is capable of DEAB-insensitive synthesis of all trans-retinoic acid. However, under steady-state and stimulated conditions in vivo, diverse bone marrow cells and peritoneal macrophages showed no evidence of intracellular RARA-activating retinoids despite expression of these enzymes and a vitamin A sufficient diet, suggesting that the enzymatic conversion of retinal is not the rate limiting step in the synthesis of intracellular RARA-activating retinoids in myeloid bone marrow cells and that that RARA remains in an un-liganded configuration during adult hematopoiesis. In order to identify additional enzymes that might contribute to DEAB-insensitive retinoid synthesis in bone marrow-derived macrophages, we compared gene expression in Kit+ progenitor cells vs bone marrow macrophages by Affymetrix array profiling. We analyzed 3 biological samples each of mouse bone marrow-derived macrophages and Kit+ progenitor cells
2015-12-17 | E-GEOD-76060 | biostudies-arrayexpress
Project description:Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages demonstrates completely divergent transcriptome profile and indicates/confirms the existance of two distinct monocyte/macrophage populations in murine bone marrow. Most resident tissue macrophages descent from embryonic precursors of the yolk sac but inflammatory and bone marrow (BM) macrophages are considered to develop from hematopoietic stem cells (HSCs) in the BM. We now identified a novel subpopulation of resident CD163+ macrophages in the BM which were phenotypically and functionally distinct from classical BM-derived macrophages. Bioinformatics analysis of transcriptoms indicated a unique immune-modulatory phenotype of CD163+ macrophages. Cell fate studies in Csf1rMer-iCre-Mer;RosaLSL-GFP mice demonstrated that resident CD163+ macrophages of the BM do not develop from HSCs but descent from embryonic progenitors in the yolk sac strictly dependent on transcription factor IRF8. In contrast to other yolk sac derived tissue macrophages CD163+ cells seem to play a relevant role in infections and sterile inflammation. IRF8-/- mice lacking this population are highly sensible to S. aureus infections. Thus, CD163 defines a macrophage population resident in the bone marrow but originating from yolk sac progenitors which exhibits immune-modulatory properties under different inflammatory conditions. We used quantitative RNA-seq to perform whole transcriptome analysis and compare the transcriptomes of resident CD163+ BM macrophages and classical CD163- BMDM in steady state and after LPS stimulation.
2017-01-31 | GSE92618 | GEO
Project description:Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. In this study, we performed gene expression profiling to examine how the transcriptional signatures compared between TSLP-elcited GMP-like cells and naïve bone marrow-resident GMPs.
2014-03-28 | GSE52485 | GEO
Project description:Macrophages are hematopoietic cells critical for innate immune defense, but also control organ homeostasis in a tissue-specific manner. Tissue-resident macrophages, therefore, provide a well-defined model to study the impact of ontogeny and microenvironment on chromatin state. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations, as well as monocytes and neutrophils. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes. Our work suggests that a combination of tissue and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment has the capacity to alter the chromatin landscape of macrophages derived from transplanted adult bone marrow in vivo and even differentiated macrophages are reprogrammed when transferred into a new tissue. Altogether, these data provide a comprehensive view of macrophage regulation and highlight the importance of microenvironment along with pioneer factors in orchestrating macrophage identity and plasticity. 7 tissue-resident macrophage populations were isolated, as well as monocytes and neutrophils, and transcriptome analysis was performed. Experiment was done in duplicates.
2014-12-05 | E-GEOD-63340 | biostudies-arrayexpress
Project description:In vivo pathways of natural retinoid metabolism and elimination have not been well characterized in primary myeloid cells, even though retinoids and retinoid receptors have been strongly implicated in regulating myeloid maturation. Using a UAS-GFP reporter transgene, and retrovirally expressed Gal4-RARA in primary mouse bone marrow cells, we identified two distinct enzymatic pathways utilized by mouse myeloid cells ex vivo to synthesize RARA ligands from free vitamin A metabolites (retinyl acetate, retinol, and retinal). Bulk Kit+ bone marrow progenitor cells utilize diethylaminobenzaldehyde (DEAB)-sensitive enzymes, whereas bone marrow-derived macrophages use DEAB-insensitive enzymes to synthesize natural RARA-activating retinoids (all-trans retinoic acid). Bone marrow-derived macrophages do not express the DEAB-sensitive enzymes Aldh1a1, Aldh1a2, or Aldh1a3, but instead express Aldh3b1, which we found is capable of DEAB-insensitive synthesis of all trans-retinoic acid. However, under steady-state and stimulated conditions in vivo, diverse bone marrow cells and peritoneal macrophages showed no evidence of intracellular RARA-activating retinoids despite expression of these enzymes and a vitamin A sufficient diet, suggesting that the enzymatic conversion of retinal is not the rate limiting step in the synthesis of intracellular RARA-activating retinoids in myeloid bone marrow cells and that that RARA remains in an un-liganded configuration during adult hematopoiesis. In order to identify additional enzymes that might contribute to DEAB-insensitive retinoid synthesis in bone marrow-derived macrophages, we compared gene expression in Kit+ progenitor cells vs bone marrow macrophages by Affymetrix array profiling.
2015-12-17 | GSE76060 | GEO
Project description:Macrophages are cells of the innate immune system fundamental to support normal haematopoiesis, fight infection, anti-cancer immunity and tumour progression. However, the function of macrophages in myeloid leukaemias remain largely unknown, due to difficulties in isolating non-transformed cells from the malignant ones. Here we use a state-of-the-art chimeric mouse of chronic myeloid leukaemia (CML) to study in the impact of the dysregulated bone marrow (BM) microenvironment on bystander macrophages. Utilising single cell RNA sequencing (scRNA seq) of Philadelphia chromosome (Ph) negative macrophages and secretome proteomics of murine c-kit+ stem/progenitor cells we have uncovered that macrophages exposed to a CML environment are altered transcriptionally and have reduced phagocytic function
2023-12-23 | PXD022366 | Pride
Project description:Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. In this study, we compare the gene expression profile of liver resident and bone marrow derived liver macrophages in mouse, 6 weeks after total body irradiation and bone marrow transplantation.
2016-07-28 | E-MTAB-4954 | biostudies-arrayexpress
Project description:Objective: Brain tumors (gliomas) contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM) biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome. Methods: High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO) database was queried to determine the prognostic value of identified microglia biomarkers in human GBM. Results: We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype. Significance: These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention. Total RNA was isolated from three independently-generated sets of flow sorted bone marrow monocytes (CD11b+ CD45high CD115+ Ly6G- cells) and brainstem microglia (CD11b+ CD45low CD115low Ly6G- cells) for Illumina RNA-Seq, and two additional pools were subsequently generated and submitted for Affymetrix Mouse Exon 1.0ST microarray. Two of the RNA-Seq samples were additionally analyzed by the microarray, for a total of 6 samples (3 monocyte, 3 microglia) in each platform. Data outputs were analyzed by two analysis methods each (RNA-Seq data: ALEXA-Seq and Cufflinks; microarray data: Partek and Aroma). All four lists were merged into a new high-confidence gene list of transcripts that were significantly differentially expressed (DE) in three out of the four analyses. In this dataset, we includeRNA-Seq data obtained from flow sorted mouse bone marrow monocytes and brainstem microglia.
2013-11-13 | E-GEOD-46688 | biostudies-arrayexpress
Project description:Objective: Brain tumors (gliomas) contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM) biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome. Methods: High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO) database was queried to determine the prognostic value of identified microglia biomarkers in human GBM. Results: We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype. Significance: These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention. Total RNA was isolated from three independently-generated sets of flow sorted bone marrow monocytes (CD11b+ CD45high CD115+ Ly6G- cells) and brainstem microglia (CD11b+ CD45low CD115low Ly6G- cells) for Illumina RNA-Seq, and two additional pools were subsequently generated and submitted for Affymetrix Mouse Exon 1.0ST microarray. Two of the RNA-Seq samples were additionally analyzed by the microarray, for a total of 6 samples (3 monocyte, 3 microglia) in each platform. Data outputs were analyzed by two analysis methods each (RNA-Seq data: ALEXA-Seq and Cufflinks; microarray data: Partek and Aroma). All four lists were merged into a new high-confidence gene list of transcripts that were significantly differentially expressed (DE) in three out of the four analyses. In this dataset, we include exon expression data obtained from flow sorted mouse bone marrow monocytes and brainstem microglia.
2013-11-13 | E-GEOD-46686 | biostudies-arrayexpress