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RNA-seq analysis of Jak2-V617F monocytes in elastic versus viscous fibrotic matrix

ABSTRACT: Myelofibrosis (MF) is a progressive, bone marrow (BM) malignancy associated with monocytosis, and is believed to promote the pathological remodelling of the extracellular matrix. Here, we show that the mechanical properties of MF, namely the liquid-to-solid properties (viscoelasticity) of BM, contribute to aberrant differentiation of monocytes. Human monocytes cultured in stiff, elastic hydrogels show pro-inflammatory polarization and differentiation towards dendritic cells, as opposed to those cultured in a viscoelastic matrix.

ORGANISM(S): Mus

PROVIDER: GSE206771 | GEO | 2022/07/11

REPOSITORIES: GEO

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Viscoelastic properties of ECM differentially regulate monocyte patterns of gene expression

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Identification of potential of new therapeutic approaches for JAK2 V617F mutant patients

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RNA-seq analysis of Jak2-V617F monocytes in elastic versus viscous fibrotic matrix

Project description:RNA-seq analysis of Jak2-V617F monocytes in elastic versus viscous fibrotic matrix

| PRJNA852159 | ENA

Clonotypic analysis of T cells cultured in extracellular matrices of different viscoelasticies

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Gene expression profiles of CD8+ T cells cultured in extracellular matrices of different viscoelasticies

Project description:The efficacy of adoptive T cell therapy is highly dependent on the generation of T cell populations that are able to both provide immediate effector function and long-term protective immunity. Inspired by the emerging consensus that T cell phenotype and function are inherently linked to their tissue localization, we present an approach to generate functionally distinct T cell populations via the physical properties of their surrounding matrix. A collagen type I based extracellular matrix (ECM) was engineered to allow for independent tuning of matrix stiffness and viscoelasticity, two features that characterize the mechanical properties of tissues. To investigate how ECM viscoelasticity drives changes in the transcriptional landscape of T cells, scRNA-seq of CD8+ T cells cultured in fast relaxing and slow relaxing collagen matrices was performed

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B-cell derived macrophage in mouse and human breast cancer macrophage

Project description:Cancer actively uses B cells to promote its progression and metastasis. For example, it causes accumulation of bone marrow (BM) B-cell precursors in spleen to convert into immunosuppressive Breg cells. Here, we provide evidence that cancer also coopts differentiation BM CSF1R+ Pax5Lo B-cell precursors to generate macrophages (termed B-MF cells). To do this, cancer uses CSF1 to trigger Csf1r signaling and downregulate PAX5 in B-cell precursors by activating FOXO1. Although tumor-associated macrophages (TAMs) are primarily derived from BM monocytes, our data suggest that some of them may have B-cell origin. Unlike monocyte-derived TAMs, B-MF exhibit a higher M2 polarization, more efficiently phagocytize apoptotic cells, induce FoxP3+ Tregs and suppress T cells activity. We propose that the cancer-B-MF axis is a novel immune escape pathway, thus a therapeutic target.

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Extracellular Matrix Viscoelasticity Promotes Liver Cancer Progression in Pre-Cirrhotic NASH

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2023-10-14 | GSE245016 | GEO

Expression data from a variant monocyte population following dendritc cell depletion

Project description:Ly6C+ ‘classical’ monocytes respond rapidly to inflammation, either directly as effector cells or by differentiating into inflammatory macrophages and dendritic cells (DC). In the absence of DC, elevated levels of serum Flt3L and G-CSF induce a monocytosis although the properties of this expanded population have not been addressed. Here, we show that depletion of DC using the CD11c-DTR model results in rapid and CCR2-independent expansion of a variant population of splenic MHC Class II+ CD64+ Ly6C+ monocytes that are distinct from both circulating blood Ly6C+ monocytes and their tissue counterparts, but resemble Ly6C+ cells mobilized by exogenous G-CSF and Flt3L. The CD64+ Ly6C+ monocyte population is characterized by up-regulation of TLR signalling apparatus and an increased capacity to produce TNF-a following stimulation. Therefore, perturbation within the mononuclear phagocytic system in the absence of inflammation induces an alternative differentiation pathway that drives expansion of monocytes poised for innate immune activation. Monocytes populations were purified from CD11c-DTR mice which were injected with PBS or diphtheria toxin 48 hours previously. Common monocyte progenitors (cMoP) were isolated from untreated C57BL/6 mice. 48 hours after injection of PBS or DT, monocytes were purified from the spleen after collagenase digestion and flow sorted directly into Qiagen RLT buffer. cMoP were purified directly from the bone marrow without digestion enzymes.

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