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GSE76999
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
- 9 Downloadable Samples
Illumina HiSeq 2500
Description
The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11c?Vhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo. VHL-deficient phenotype is intrinsic in AMs derived from monocyte precursors in mixed bone marrow chimeras. Moreover, unlike control Vhlfl/fl, AMs from CD11c?Vhl mice do not revert pulmonary alveolar proteinosis when transplanted into Csf2rb-/- mice, demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our results suggest that optimal AM terminal differentiation, self-renewal, and homeostatic function requires their oxygen sensing capacity. Overall design: BAL AMs were pooled from 5-7 age and sex-matched mice per genotype and further purified by positive selection with anti-CD11c-microbeads (Miltenyi Biotec), following manufacturer's instructions. Cell lysis was performed with buffer RLT (Qiagen), containing 10µ/ml ß-mercaptoethanol and RNA was isolated with RNeasy Plus Mini Kit (Qiagen). RNA concentration and integrity were determined with an Agilent 2100 Bioanalyzer (Caliper Life Science). Samples with RNA integrity values > 8 were further processed. A total of 3 pools per genotype were used for RNA Seq.
Publication Title
Von Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal Differentiation, Self-Renewal, and Function.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Numerous CD11b+ myeloid cells are present within the dermis. They are very heterogeneous and can be divided in dermal DCs, tissue monocytes and tissue macrophages. At steady state, only CD11b+ DC migrate from the dermis to the skin draining lymph nodes whereas upon DNFB-induced inflammation, CD11b+ DC as well as dermal monocytes migrated to the lymph nodes. The objective of this study was to use gene expression profiling to rigorously identify the different subsets of dermal CD11b+ myeloid cells at steady state and upon inflammation and to characterize their functional potential.
Publication Title
Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin.
Sample Metadata Fields
Sex, Age, 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
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
To find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Publication Title
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Nephron progenitor cells generate nephrons, the basic units of kidney. We developed methods to culture mouse and human NPCs in their self-renewal state in vitro with full nephrogenic potentials. The RNA-seq here is used to compare the global gene expression of long-term cultured mouse NPCs and their cognate freshly isolated primary NPCs Methods: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line). To generate rpkm values from raw data, single-end 50bp reads were mapped to the UCSC mouse transcriptome (mm9) by STAR9, allowing for up to 10 mismatches (which is the default by STAR). Only the reads aligned uniquely to one genomic location were retained for subsequent analysis. And expression levels of all genes were estimated by Cufflink10 using only the reads with exact matches. Results: The gene expression levels of the "NPC-signature genes" were firstly transformed as logarithm scales. And then the program “prcomp”, a built-in program for principal component analysis in R packages, was employed with default parameters. We evaluated the variance percentage of each principal component, and found the top 3 components accounted for 84.1% of the total variance, where PC1 accounted for 46.42%, PC2 23.87% and PC3 13.81%. Those three PCs are therefore selected as candidate principal components in the further analysis. Another program “scatterplot3d” in the R packages was used to plot the 3D view of PCA, and “ggplot2” was used in 2D view of PCA. The PCA results indicate that cultured NPCs cluster together in PCA analysis while primary NPCs segregate into early (E11.5 to E13.5) and later (E16.5, P1) NPC groups. Interestingly, cultured NPCs are close to early NPCs in both PC1 and PC2 axes, suggesting that cultured NPCs are maintained in state close to early NPCs. The close cluster of P20 and P80 NPCs show the robustness of our culture condition in maintaining stable self-renewal state of NPCs. Conclusions: Our study represents the first analysis comparing the long-term cultured NPC lines we geneated with primary NPCs, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line)
Publication Title
3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.
Sample Metadata Fields
Specimen part, Cell line, Subject
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