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GSE144708
Mus musculus
25 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We performed ontogenic, transcriptomic and spatial characterization of sciatic nerve Macs (snMacs). Using multiple fate-mapping systems, we show that snMacs do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursors and get replaced by bone marrow-derived Macs over time. Using single-cell profiling, we identified a tissue-specific core signature of snMacs and found two spatially-separated snMacs: Relmα + Mgl1 + snMacs in the epineurium and Relmα Mgl1 snMacs in the endoneurium. Globally, snMacs lack most core signature genes of microglia, with only the endoneurial subset expressing a restricted number of these genes. Single-cell transcriptomics revealed that in response to injury both snMacs respond differently and that the PNS, in contrast to the CNS, is permissive to prolonged engraftment of monocyte-derived Macs recruited upon injury.
Publication Title
Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages.
Publication Title
Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.
Publication Title
Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression. Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression.
Publication Title
The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microarray, Bulk RNA Sequencing and Single cell RNA Sequencing of different murine tissue-resident macrophage populations to assess role of Zeb2 and LXRa
Publication Title
The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.
Publication Title
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 62 Downloadable Samples
Illumina HiSeq 4000
Description
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain. Overall design: sample of WT choroid plexus, sample of WT dura mater, sample of WT enriched SDM, sample of WT whole brain, sample of 9 months old APP/PS1 mice, sample of 16 months old APP/PS1 mice, sample of 16 months old WT mice, sample of Irf8 KO whole brain, sample of Irf8 KO choroid plexus, sample of Irf8 WT whole brain, sample of Irf8 WT choroid plexus, sample of dura mater with standard protocol and with ActD protocol, sample of choroid plexus with standard protocol and ActD protocol.
Publication Title
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples