Macrophages are metabolically heterogenous within the tumor microenvironment
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ABSTRACT:
PROVIDER: PRJNA779399 | ENA |
REPOSITORIES: ENA
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Project description:Macrophages are often prominently present in the tumor microenvironment, where distinct macrophage populations can differentially affect tumor progression. Although metabolism influences macrophage function, studies on the metabolic characteristics of ex vivo tumor-associated macrophage (TAM) subsets are rather limited. Using transcriptomic and metabolomic analyses, we now reveal that pro-inflammatory MHC-IIhi TAMs display a hampered TCA cycle, while reparative MHC-IIlo TAMs show a higher oxidative and glycolytic metabolism. Although both TAM subsets rapidly exchange lactate in high lactate conditions, only MHC-IIlo TAMs use lactate as an additional carbon source. Accordingly, lactate supports the oxidative metabolism in MHC-IIlo TAMs, while it decreased the metabolic activity of MHC-IIhi TAMs. Lactate subtly affected the transcriptome of MHC-IIlo TAMs, increased L-arginine metabolism and enhanced T-cell suppressive capacity of these TAMs. Overall, our data uncover the metabolic intricacies of distinct TAM subsets and identify lactate as a carbon source, and metabolic and functional regulator of TAMs.
2021-11-12 | GSE188549 | GEO
Project description:Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function. We used microarray to support proteomic data between M1 and M2 macrophages. M1 macrophages are obtained using cell sorting of CD45+MHCII+CD8a-F4/80+ population from C57BL/6J bone marrow cell derived heterogenous cells under GM-CSF conditioning for 7 days. M2 macrophages are differentiated with 20% L929 cell supernatant for 7 days and sorted from CD45+F4/80+CD11b+ population.
2014-11-14 | E-GEOD-63245 | biostudies-arrayexpress
Project description:Single-Cell RNA Sequencing Uncovers Heterogenous Transcriptional Signatures in Macrophages during Efferocytosis
| PRJNA658604 | ENA
Project description:Efferocytosis triggers cellular reprogramming, including the induction of mRNA transcripts which encode anti-inflammatory cytokines that promote inflammation resolution. Our current understanding of this transcriptional response is largely informed from analysis of bulk phagocyte populations; however, this precludes the resolution of heterogeneity between individual macrophages and macrophage subsets. Moreover, phagocytes may contain so called “passenger” transcripts that originate from engulfed apoptotic bodies, thus obscuring the true transcriptional reprogramming of the phagocyte. To define the transcriptional diversity during efferocytosis, we utilized single-cell mRNA sequencing after co-cultivating macrophages with apoptotic cells. Importantly, transcriptomic analyses were performed after validating the disappearance of apoptotic cell-derived RNA sequences. Our findings reveal new heterogeneity of the efferocytic response at a single-cell resolution, particularly evident between F4/80+ MHCIILO and F4/80- MHCIIHI macrophage sub-populations. After exposure to apoptotic cells, the F4/80+ MHCIILO subset significantly induced pathways associated with tissue and cellular homeostasis, while the F4/80- MHCIIHI subset downregulated these putative signaling axes. Ablation of a canonical efferocytosis receptor, MerTK, blunted efferocytic signatures and led to the escalation of cell death-associated transcriptional signatures in F4/80+ MHCIILO macrophages. Taken together, our results newly elucidate the heterogenous transcriptional response of single-cell peritoneal macrophages after exposure to apoptotic cells.
2020-08-22 | GSE156234 | GEO
Project description:MoS2 has found application in various biomedical fields, such as bioimaging and drug delivery. Nonetheless, utilizing MoS2 for anti-tumor therapy remains challenging, especially tumor immunotherapy. Macrophages, pivotal constituents of the tumor microenvironment, play a crucial role in driving tumor progression and chemoresistance. Modulating macrophages to reshape this microenvironment stands as a promising avenue for effective tumor treatment. In this study, we unveil a mechanism by which MoS2 induces the metamorphosis of macrophages from an M0 to an M1 phenotype, thus altering the tumor microenvironment. This transformation triggers pathways associated with inflammation within M1-type macrophages, leading to an upsurge in the expression of inflammatory molecules like IL1β. Macrophages activated by MoS2 exhibit a propensity to impede tumor cell proliferation. Through comprehensive RNA-sequencing analysis, we noted that MoS2 induces a greater enrichment of differentially expressed genes in the cytokine release pathway within macrophages. The excessive secretion of IL1β by MoS2-activated macrophages emerges as a pivotal catalyst, heightening ROS levels and decreasing GSH levels within tumor cells, ultimately culminating in ferroptosis. Therefore, we suggest MoS2 effectively reshapes the tumor microenvironment by steering macrophages toward releasing inflammatory molecules. The MoS2-triggered activation of macrophages, inducing the secretion of IL1β, emerges as a potent trigger for ferroptosis within tumor cells. Consequently, MoS2 holds substantial promise as an efficacious strategy for anti-tumor immunotherapy, achieved through the polarization of macrophages.
2023-12-31 | GSE251769 | GEO
Project description:We performed spatial transcriptome profiling (ST-seq) on nine fresh frozen tissue sections to understand the immunophenotypes; immune cell types, states and their spatial location within the clear cell renal cell carcinoma (ccRCC) tumour microenvironment (TME).
2023-08-16 | E-MTAB-12767 | biostudies-arrayexpress
Project description:The authors previously suggested that CD204 was a useful marker for tumor-associated macrophages (TAMs) of esophageal squamous cell carcinoma (ESCC). In this study, they discovered that within ESCC microenvironment not only cancer cells but also TAMs expressed cysteine-rich, angiogenic inducer, 61 (Cyr61), induced by conditioned media of ESCC cells. Levels of Cyr61 expression were associated with CD204+ macrophage infiltration in ESCC tissue. Cyr61 promoted CD204 expression and migration of macrophages via MEK/Erk pathway in vitro.
2014-10-08 | GSE59471 | GEO
Project description:Small RNA deep sequencing analysis on the microRNA components within exosomes secreted from adipose tissue macrophages of lean and obese mice
2017-09-01 | GSE97652 | GEO
Project description:Molecular mechanisms of the cancer cells-macrophages interactions growing in vitro conditions as a co-culture. The five canine mammary cancer cell lines were cultured with monocytes sorted from the canine blood for 72hrs. Then, the cancer cells and macrophages were sorted and the gene expression analysis was conducted. The control for each co-cultured cell line was the same cell line growing as a single culture, whereas the control for the macrophages growing in a co-culture conditions were macrophages growing as a single culture. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Dye-swap experiment, each cell line growing in the co-culture conditions was compared to the same cell line growing as a single culture, macrophages growing in the co-culture conditions were compared to the macrophages growing as the single culture.
2012-05-30 | E-GEOD-29339 | biostudies-arrayexpress
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