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RNASeq of bone lining niche cell components from healthy vs. myeloma-bearing mice

ABSTRACT: RNASeq of bone lining niche cell components from healthy vs. myeloma-bearing mice

PROVIDER: PRJNA559729 | ENA |

REPOSITORIES: ENA

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RNASeq of bone lining niche cell components from healthy vs. myeloma-bearing mice

Project description:We compare gene expression in FACS-sorted bone-lining cell components: stromal progenitors, osteoprogenitors and endothelial cells, from myeloma-bearing vs. from healthy mice, and also between myeloma cells flushed from the central bone marrow vs. myeloma cells digested from the bone surface (myeloma-bearing mice only). The myeloma model used is the 5TGM1 murine myeloma cell line, injected into immunocompetent KaLwRij mice.

2019-08-14 | GSE135691 | GEO

RNASeq of bone lining niche cell components from myeloma-bearing mice treated daily with small molecule LDN193189 (LDN) or vehicle control

Project description:We compare gene expression in FACS-sorted bone lining cell components (stromal progenitors, osteoprogenitors, endothelial cells) from LDN193189 vs. vehicle-treated myeloma-bearing mice, and in myeloma cells flushed from the central marrow vs. myeloma cells digested from the bone-lining niche. The myeloma model used is the murine 5TGM1 cell line injected into immunocompetent KaLwRij mice. LDN193189 is a type 1 BMP receptor inhibitor.

2019-08-14 | GSE135785 | GEO

RNASeq of bone lining niche cell components from myeloma-bearing mice treated daily with small molecule LDN193189 (LDN) or vehicle control

Project description:RNASeq of bone lining niche cell components from myeloma-bearing mice treated daily with small molecule LDN193189 (LDN) or vehicle control

| PRJNA560057 | ENA

Osteoclasts Control Re-activation of Dormant Myeloma Cells by Remodeling the Endosteal Niche

Project description:Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched ‘on’ by engagement with bone lining cells or osteoblasts, and switched ‘off’ by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.

2015-11-30 | GSE57695 | GEO

Transcriptomic profiling of the myeloma bone-lining niche identifies BMP signalling as a target for bone disease

Project description:Transcriptomic profiling of the myeloma bone-lining niche identifies BMP signalling as a target for bone disease

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Niche modulated versus niche modulating genes in multiple myeloma

Project description:Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown. Design and Methods. BM aspiration samples were obtained from MM-patients with a high tumor load. Gene expression profile (GEP) was recorded immediately following aspiration and at subsequent time points. Identification of niche-regulated genes relied on spontaneous gene modulation following loss of niche regulation. Results. Compared to the reference samples fixed immediately following aspiration, the BM samples fixed after longer delay acquired numerous changes in GEP. The top modulated genes included a common subset of ~ 60 genes displaying prompt and sustained “switch” in expression consistently, among which were oncogenes (FOS, JUN) and genes regulating homing (CD69, RGS1), expansion and angiogenesis (AREG, PTGS2, RGS2, NR4A2). Interestingly, the “switch” in GEP was reversible and turned “off” and “on” in culture conditions resuming cell-cell-matrix contact versus re-spread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of the tumor cells out-of-niche and the regression of the “contactless switch” was followed by induction of a new set of genes this time mostly encoding extracellular proteins, including angiogenic factors (IL8, CXCL5), extracellular-matrix proteins (SPP1, FN1), chemokines (CXCL5, CCL2, CCL20) and growth factors (CCL2, IL6). Conclusions. Our dataset, being unique in authentic expression design, uncovered contact-regulated genes capable of controlling homing, expansion and tumorigenesis. The adaptive response of the tumor cells to culture conditions deficient of integral niche components (e.g., vascular vessels) uncovered inducible niche-regulating tumor genes.

2012-02-23 | GSE36036 | GEO

scRNAseq of the bone marrow immune microenvironment in control and 5TGM1 myeloma-bearing C57Bl/6 and KaLwRij mice

Project description:We hypothesized that the immune microenvironment of the bone marrow influences the progression of myeloma outgrowth in the 5TGM1 transfer model of multiple myeloma. Therefore we sorted bone marrow T, B, NK, neutrophils, and monocytes/macrophages from control and tumor-bearing C57Bl/6 and KaLwRij mice.

2023-02-23 | E-MTAB-12616 | biostudies-arrayexpress

Synergistic, context-dependent and hierarchical functions of hematopoietic progenitor niche components.

Project description:Specialized niche environments specify and maintain stem and progenitor cells, but little is known about the identities and functional interactions of niche components in vivo. Here, we describe a modular system for the generation of artificial hematopoietic niches in the mouse embryo. A circumscribed tissue that lacks niche function but is physiologically accessible for hematopoietic progenitor cells is functionalized by individual and combinatorial expression of four factors, the chemokines Ccl25 and Cxcl12, the cytokine Scf and the Notch ligand DLL4. The distinct phenotypes and variable numbers of hematopoietic cells in the resulting niches reveal synergistic, context-dependent and hierarchical interactions among niche effector molecules. The surprisingly simple rules determining niche outcomes enable the in vivo engineering of artificial niches conducive to the presence of distinct myeloid or T or B lymphoid lineage precursors. The dataset comprises 24 samples divided into eight sample groups each representing a different lymphoid progenitor cell type isolated from wild-type (+/-) or transgenic (-/-) thymic niches. -/-, Foxn1-deficient genotype; +/-, Foxn1 heterozygous phenotype; DP, CD4/CD8 double-poisztive thymocytes; DN3, CD4/CD8-negative stage 3 thymocytes; SP4, CD4 single-positive thymocytes; SP8, CD8 single-positive thymocytes; B IgM-, IgM surface negative B cells; B IgM+, IgM surface positive B cells; B IgM- -/-, IgM surface negative B cells from Foxn1-deficient genotype.

2012-08-24 | E-GEOD-33268 | biostudies-arrayexpress

Bulk RNAseq of control and 5TGM1 myeloma-bearing bone marrow T, NK, and non-hematopoietic stromal cells from C57Bl/6 mice

Project description:We hypothesized that the immune microenvironment of the bone marrow influences the progression of myeloma outgrowth in the 5TGM1 transfer model of multiple myeloma. Therefore we sorted bone marrow T, NK, and non-hematopoietic stromal cells from control and tumor-bearing C57Bl/6 mice.

2023-02-24 | E-MTAB-12615 | biostudies-arrayexpress

Synergistic, context-dependent and hierarchical functions of hematopoietic progenitor niche components.

2012-08-24 | GSE33268 | GEO

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