Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA-sequencing resolves IL-4 and IFN-γ into distinct inflammatory trajectories within GM-CSF macrophages

ABSTRACT: To account for the within-state heterogeneity of GM-CSF compared to M-CSF macrophages (Helft et al. 2015), we performed multiplexed scRNA-seq on 49,441 GM-CSF–derived macrophages stimulated with IL‑4, IFN‑γ, IL‑10, or TGF‑β. Cells were visualized by principal component analysis (PC1 = 13.21%, PC2 = 4.65%), which recapitulated patterns previously observed in bulk RNA-seq. IL‑4 displaced cells farthest along PC1 towards a cell cluster enriched for NfkB controlled gene expression with high Ccl22 and Ccr7, consistent with a dendritic‑cell‑like, T‑cell‑activating phenotype. IFN‑γ dominated PC2, retaining high MHC-II expression while adding a complement/interferon module (C1qb, C1qc, Gbp2, Irf1), and showed enrichment for IRF1/8 and STAT1 transcription factor signatures. TGF‑β and IL‑10 co-clustered in the PC1/PC2 low quadrant and shared expression of reparative markers including Chil3 and Cd24, forming an immunosuppressive, trophic branch distinct from either inflammatory pole. Together, these data show that within the GM-CSF lineage, IL‑4 and IFN‑γ drive orthogonal inflammatory trajectories, whereas IL‑10 and TGF‑β consolidate a shared remodeling program.

ORGANISM(S): Mus musculus

PROVIDER: GSE304596 | GEO | 2025/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cytokine–ontogeny interaction shapes macrophage transcriptional states (GM-CSF–derived macrophages)

Project description:In GM-CSF–derived macrophages, bulk RNA-seq was performed on five biological replicates per cytokine condition (IL‑4, IFN‑γ, IL‑10, TGF‑β). IL‑4 separated along PC1 (47% variance) but showed no additional Hallmark enrichment. PC2 (25% variance) distinguished the IFN‑γ pole characterized by IRF1/STAT1-regulated genes (Gbp genes, Cxcl9), from IL‑4 and IL‑10/TGF‑β poles, denoting distinct remodeling programs. These data establish an ontogeny‑dependent divergence at the transcriptomic level.

2025-09-30 | GSE304645 | GEO

Cytokine–ontogeny interaction shapes macrophage transcriptional states (M-CSF–derived macrophages)

Project description:In M-CSF–derived macrophages, bulk RNA-seq was performed on five biological replicates per cytokine condition (IL‑4, IFN‑γ, IL‑10, TGF‑β). IL‑4 dominated PC1 (54% variance) driving a reparative module with EMT, UPR, and mTORC1 signatures, while IFN‑stimulated genes (Gbp4, Ifi44) were repressed. PC2 (26% variance) spanned an inflammatory‑to‑remodeling continuum: IFN‑γ anchored the chemokine‑rich, IFN‑responsive pole (Ccl7, Ccl2, Ccl12), whereas TGF‑β anchored a matrix‑remodeling/angiogenic pole (Mmp14, Cav1, Cspg4); IL‑10 shifted modestly toward the IFN‑low quadrant.

2025-09-30 | GSE304647 | GEO

Cytokine–ontogeny interaction shapes macrophage transcriptional states (combined GM-CSF– and M-CSF–derived macrophages)

Project description:We generated eight macrophage states using a cytokine–ontogeny matrix, combining two macrophage ontogenies (M-CSF and GM-CSF) with four cytokines (IL‑4, IFN‑γ, IL‑10, TGF‑β). Bulk RNA‑seq on five biological replicates per condition revealed that PC1 (54% variance) segregated ontogeny: GM‑CSF states loaded negatively, M‑CSF states positively. Gene‑set enrichment analysis of negative PC1 loadings highlighted NfkB programs, confirming the intrinsic inflammatory bias of GM‑CSF macrophages (Hamilton 2008; Hamilton et al. 2016)

2025-09-30 | GSE304646 | GEO

Cytokine–ontogeny interaction shapes macrophage transcriptional states

Project description:Macrophage ontogeny and local cytokines jointly govern tumor-associated macrophage behaviour, yet how these signals integrate to generate pro- or antitumor outputs is unknown. Here, we apply a reductionist, multi-scale pipeline to systematically map eight reference macrophage states generated by ex vivo differentiation of mouse bone marrow cells with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) and subsequent cytokine polarization (IFN-gamma, IL-4, IL-10, TGF-beta). We integrated transcriptomic, 3D spheroid, and in vivo metastatic analyses to discover a lineage dependent polarity switch: IL-4 drives an ARG1+, tumor-supportive programme in M-CSF macrophages but, via NfkB, induces a CCR7+ inflammatory phenotype in GM-CSF macrophages. IFN-gamma uniformly activates STAT1/IRF pathways, maintaining antitumor profiles, whereas IL-10 and TGF-beta maximally evoke SPP1+ immunosuppressive signatures after GM-CSF priming. Functional assays confirmed these transcriptional states dictate opposite effects on tumor growth, invasion, and pulmonary metastasis. Integration of all parameters yielded an "ontogeny cytokine code" that predicts macrophage function based on developmental history and cytokine milieu. Identifying CSF-defined lineage as a master regulator of macrophage heterogeneity provides a blueprint for precision immunotherapies that reprogram macrophages in solid tumors. This SuperSeries is composed of the SubSeries listed below.

2025-09-30 | GSE304868 | GEO

Interferon-gamma critically determines dendritic cell function

Project description:A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects IFN-gamma on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that following differentiation of human peripheral-blood monocytes into moDCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, interferon-gamma (IFN-gamma) induces moDC maturation and up-regulates the co-stimulatory markers CD80, CD86, CD95, and MHC Class I, enabling moDCs to effectively generate antigen-specific CD4+ and CD8+ T cell responses for multiple viral and tumor antigens. Interestingly, early exposure of monocytes to high concentrations of IFN-gamma promotes monocyte differentiation into macrophages, despite the presence of GM-CSF and IL-4. However, under low concentrations of IFN-gamma, monocytes continue to differentiate into dendritic cells possessing a unique gene-expression profile, resulting in impairments in subsequent maturation by IFN-gamma and an inability to generate effective antigen-specific CD4+ and CD8+ T cell responses compared to standard moDCs. Monocytes differentiated in the presence of low levels of IFN-gamma downregulate IFN-gamma receptor expression, impairing their response to an inflammatory rechallenge. These findings demonstrate the ability of IFN-gamma to impart differential programs on human moDCs which shape the antigen-specific T cell responses they induce. Timing and intensity of exposure to IFN-gamma can thus determine whether moDCs are tolerogenic or immunostimulating. Human monocyte-derived dendritic cells from 4 healthy donors were differentiated with either GM-CSF and IL-4 (n=4) or GM-CSF, IL-4, and IFN-gamma (n=4). These samples were subsequently hybridized to arrays as 4 biological repeats for each of the two treatment conditions.

2014-06-01 | E-GEOD-47621 | biostudies-arrayexpress

Single cell immune profiling reveals a developmentally distinct CD4+ GM-CSF+ T cell lineage that induces GI tract GVHD

Project description:Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft versus host disease (GVHD). CD4+ T cells that produce GM-CSF have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if there exists a unique CD4+ GM-CSF+ subset that differs from other defined T helper (TH) subtypes. Using single cell RNA sequencing analysis, we identified two CD4+ GM-CSF+ T cell populations that arose during GVHD and were distinguishable by the presence or absence of IFN-γ co-expression. CD4+ GM-CSF+ IFN-γ- T cells which emerged preferentially in the colon had a distinct transcriptional profile, employed unique gene regulatory networks, and possessed a non-overlapping TCR repertoire when compared to CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T cell populations in the colon. Functionally, this CD4+ GM-CSF+ T cell population contributed to pathological damage in the GI tract which was critically dependent upon signaling through the IL-7 receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic TH GM-CSF+ subset that mediates immunopathology.

2022-01-14 | GSE193475 | GEO

The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells

Project description:Interleukin-21 (IL-21) has broad actions on T- and B-cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive-transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon (IFN)-γ-producing CD4+ T cells in Il21r-/-Rag2-/- mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2-/- mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.

2013-02-14 | GSE27161 | GEO

Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Project description:Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.

2023-05-12 | GSE203220 | GEO

Human monocyte-derived dendritic cells: Control vs Tolerogenic

Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1)

2009-11-13 | GSE18921 | GEO

Interferon-gamma critically determines dendritic cell function

2014-06-01 | GSE47621 | GEO