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Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors

ABSTRACT: Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors

PROVIDER: PRJNA926671 | ENA |

REPOSITORIES: ENA

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Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors

Project description:Melanomas display high numbers of tumor-associated macrophages (TAMs), which correlate with worse prognosis but also retain the potential to restore anti-tumor activity. Harnessing macrophages for therapeutic purposes has been particularly challenging due to their heterogeneity, based on their ontogeny and function and driven by the tissue-specific niche. In the present study, we used the YUMM1.7 murine melanoma model to better understand melanoma TAM origin and dynamics during tumor progression, with potential therapeutic implications. We identified distinct TAM subsets based on F4/80 expression, with the F4/80high fraction increasing over time and displaying tissue-resident-like phenotype. While skin-resident macrophages showed mixed ontogeny, F4/80+ TAM subsets in i.d. YUMM1.7 tumors originated almost exclusively from bone-marrow precursors. Multiparametric analysis of macrophage phenotype showed a temporal divergence of F4/80+ TAM subpopulations, which also differed from skin-resident subsets, and from their monocytic precursors. Overall, F4/80+ TAMs displayed co-expression of M1- and M2-like canonical markers, and RNA-seq and pathway analysis showed differential immunosuppressive and metabolic profiles. GSEA showed F4/80high TAMs to rely on oxidative phosphorylation, with increased proliferation and protein secretion while F4/80low cells had high pro-inflammatory and intracellular signaling pathways, with lipid and polyamine metabolism. Overall, the present in-depth characterization provides further evidence of the ontogeny of the evolving melanoma TAMs. Some of these gene profiles matched recently-identified TAM clusters in other tumor models and human cancers, which in turn can lead to more effective therapies targeting specific immunosuppressive cells in advanced tumor stages.

2023-01-30 | GSE223545 | GEO

Whole genome bisulfite sequencing of bovine morula derived from metabolically divergent dairy cows

Project description:Whole genome bisulfite sequencing of bovine morula derived from metabolically divergent dairy cows

| PRJEB33956 | ENA

Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells

Project description:Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells

| PRJNA976184 | ENA

Whole genome bisulfite sequencing of bovine morula derived from metabolically divergent dairy cows

Project description:Lactating cows experience transient metabolic stresses during postpartum which results in abnormal concentrations of non-esterified fatty acids and beta-hydroxybutyrate that can affect embryo-maternal communication and ultimately reproductive success. We hypothesize that metabolic challenges in lactating cows influence DNA methylation changes of the embryos prior to implantation affecting genes involved in embryo developmental competency. Therefore, we compared whole genome bisulfite sequencing (wgbs) of morulas derived from in vitro produced 2-4 cell embryos and transferred in the oviduct of metabolically profiled lactating cows until day 7. Similar stage of in vitro production (IVP) embryos were transferred to the oviduct of nulliparous heifers as a metabolically unchallenged control. Bisulfite-Seq DNA libraries were generated from groups of five morulas using an EZ DNA methylation-direct kit and Pico-Methyl seq library preparation kit (Zymo Research), and parallel sequenced using the illumine HiSeq2500 system at the institute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.

2021-11-30 | E-MTAB-8239 | biostudies-arrayexpress

Whole genome bisulfite sequencing of bovine oocytes from metabolically divergent lactating cows and nulliparous heifers

Project description:Whole genome bisulfite sequencing of bovine oocytes from metabolically divergent lactating cows and nulliparous heifers

| PRJEB33720 | ENA

Whole genome bisulfite sequencing of bovine oocytes from metabolically divergent lactating cows and nulliparous heifers

Project description:Lactating cows experience transient metabolic stresses during postpartum which results in abnormal concentrations of non-esterified fatty acids and beta-hydroxybutyrate that can impact oocyte maturation and ultimately reproductive success. We hypothesize that metabolic challenges in lactating cows influence DNA methylation changes of the oocyte affecting genes involved in oocyte developmental competency. Therefore, we compared whole genome bisultfite sequencing (wgbs) of the oocytes collected from 5-6 week (early) or 9-10 week (mid) post-partum against that of oocytes from nulliparous heifers as metabolically unchallenged condition control. Bisulfite-Seq DNA libraries were generated from pooled oocytes using an EZ DNA methylation-direct kit and Pico-Methyl seq library preparation kit (Zymo Research), and parallel sequenced using the illumina HiSeq2500 system.

2021-11-30 | E-MTAB-8191 | biostudies-arrayexpress

RNA-seq of liver from pigs divergent in feed efficiency highlights shifts in macronutrients metabolism, hepatic growth and immune response

Project description:Liver is a metabolically complex organ that influences nutrient partitioning and potentially modulates the efficiency of converting energy acquired from macronutrients ingestion into a muscle and/or adipose tissue (referred to as feed efficiency, FE). The objective of this study was to sequence the hepatic tissue transcriptome of pigs divergent for FE and identify relevant biological processes that underpin the differences in liver phenotypes and FE.

2019-02-11 | E-MTAB-6256 | biostudies-arrayexpress

Multiple distinct small RNAs originate from the same microRNA precursors.

Project description:MicroRNAs (miRNAs), which originate from precursor transcripts with stem-loop structures, are essential gene expression regulators in eukaryotes.We report 19 miRNA precursors in Arabidopsis that can yield multiple distinct miRNA-like RNAs in addition to miRNAs and miRNA*s. These miRNA precursor-derived miRNA-like RNAs are often arranged in phase and form duplexes with an approximately two-nucleotide 3'-end overhang. Their production depends on the same biogenesis pathway as their sibling miRNAs and does not require RNA-dependent RNA polymerases or RNA polymerase IV. These miRNA-like RNAs are methylated, and many of them are associated with Argonaute proteins. Some of the miRNA-like RNAs are differentially expressed in response to bacterial challenges, and some are more abundant than the cognate miRNAs. Computational and expression analyses demonstrate that some of these miRNA-like RNAs are potentially functional and they target protein-coding genes for silencing. The function of some of these miRNA-like RNAs was further supported by their target cleavage products from the published small RNA degradome data. Our systematic examination of public small-RNA deep sequencing data from four additional plant species (Oryza sativa, Physcomitrella patens, Medicago truncatula and Populus trichocarpa) and four animals (Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila) shows that such miRNA-like RNAs exist broadly in eukaryotes.We demonstrate that multiple miRNAs could derive from miRNA precursors by sequential processing of Dicer or Dicer-like proteins. Our results suggest that the pool of miRNAs is larger than was previously recognized, and miRNA-mediated gene regulation may be broader and more complex than previously thought.

| S-EPMC2945783 | biostudies-literature

Myeloid cells in liver and bone marrow acquire a functionally distinct inflammatory phenotype during obesity-related steatohepatitis

Project description:Liver myeloid leukocytes and their bone marrow precursors adapt a common and functionally relevant inflammatory signature during NAFLD progression.

2019-06-02 | GSE131834 | GEO

GomezElisa_AgilentMouse

Project description:Macrophages and dendritic cells (DC) are key components of cellular immunity and, as per the current model, originate from hemopoietic stem cells (HSCs). However, microglia were recently shown to originate from precursors that precede the appearance of HSCs. We thus re-investigated macrophage development and their relationship to HSCs and yolk sac (YS) precursors.

2012-03-15 | E-MEXP-3510 | biostudies-arrayexpress

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