Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bone Marrow Stromal Cells Induce Chromatin Remodeling in Multiple Myeloma Cells Leading to Transcriptional Changes [Multiome (10X Genomics) - scRNA-Seq & scATAC-Seq]

ABSTRACT: The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263178 | GEO | 2024/04/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma

Project description:Neutrophils are the most abundant nucleated cell type in the bone marrow. A pro-tumor bias in this cell type may have implications for bone-marrow residing malignancies, such as multiple myeloma. Here, we generated single cell transcriptomic overviews of the entire myeloid compartment, including the entire neutrophilic lineage, of the bone marrow of 6 newly diagnosed myeloma patients, 5 treated myeloma patients and 4 non-cancer controls. We find dat mature neutrophils in myeloma patients, both newly diagnosed and treated, have an activated and pro-inflammatory phenotype, accompanied by increased transcription of pro-inflammatory cytokines, such as IL-1β, and myeloma cell survival factors, such as BCMA-ligand BAFF/TNFSF13B. Moreover, inflammatory stromal cells can activate naive neutrophils to acquire an inflammatory phenotype as is seen in patients. Previously, we have shown that inflammatory stromal cells characterized the bone marrow of newly diagnosed myeloma patients. Here, we generate single cell RNA sequencing dataset of non-hematopoietic bone marrow cells of patients after induction treatment, high-dose melphalan, stem cell transplantation and consolidation treatment. We show that this intensive treatment reduced, but did not normalize, stromal inflammation.

2023-03-31 | E-MTAB-12760 | biostudies-arrayexpress

Genome-wide profiling of tumor cells in multiple myeloma

Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. They share a common bone marrow microenvironment with myeloma tumor cells. CD138+ tumor plasma cells from 12 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. Tumor cells were derived from single-cell suspensions of bone marrow (BM) aspirates from newly diagnosed MM patients, and RNA was extracted for microarray hybridization.

2011-04-02 | E-GEOD-28327 | biostudies-arrayexpress

Paired scRNAseq of the and non-hematopoietic and the immune microenvironment of aspirates from newly diagnosed Multiple Myeloma patients versus non-cancer controls

Project description:By generating a paired single cell RNA-sequencing database of the tumor niche from 10 newly diagnosed MM patients, we created a unique dataset allowing the in-depth analyses of stromal-immune interactions within the tumor microenvironment. Using this database, we identified the presence of inflammatory stromal fibroblasts in the bone marrow of Myeloma patients.The stromal inflammation was associated with NF-κB signaling, and sources of IL-1β or TNFα were specific immune subsets previously shown to be altered in MM, suggesting the presence of an immune cell-mediated feed-forward loop of bone marrow inflammation in MM. By tracking inflammatory signatures over time in individual patients undergoing first-line treatment using bulk RNA sequencing, we show that bone marrow inflammation is not reverted by successful anti-tumor therapy (see related accession number), suggesting a role for stromal fibroblasts and bone marrow inflammation in disease persistence or relapse.

2020-09-30 | E-MTAB-9139 | biostudies-arrayexpress

RNA sequencing of the non-hematopoietic microenvironment of aspirates from Multiple Myeloma patients at diagnosis and after treatment versus non-cancer controls

Project description:By generating a paired single cell RNA-sequencing database of the tumor niche from 10 newly diagnosed MM patients, we created a unique dataset allowing the in-depth analyses of stromal-immune interactions within the tumor microenvironment (see related accession number). Using this database, we identified the presence of inflammatory stromal fibroblasts in the bone marrow of Myeloma patients.The stromal inflammation was associated with NF-κB signaling, and sources of IL-1β or TNFα were specific immune subsets previously shown to be altered in MM, suggesting the presence of an immune cell-mediated feed-forward loop of bone marrow inflammation in MM. By tracking inflammatory signatures over time in individual patients undergoing first-line treatment using bulk RNA sequencing, we show that bone marrow inflammation is not reverted by successful anti-tumor therapy (this dataset), suggesting a role for stromal fibroblasts and bone marrow inflammation in disease persistence or relapse. Raw sequencing data files will be deposited to EGA.

2021-02-01 | E-MTAB-9285 | biostudies-arrayexpress

Genome-wide profiling of tumor cells in multiple myeloma

2011-04-02 | GSE28327 | GEO

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

2018-10-24 | PXD006581 | Pride

Transcription profiling of human plasma cell samples from multiple myeloma patients before treatment

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Baseline gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation

2008-04-07 | E-GEOD-4204 | biostudies-arrayexpress

Transcription profiling of human newly diagnised multiple myeloma patients prior to treatment

2008-06-13 | E-GEOD-4452 | biostudies-arrayexpress

Transcription profiling of human multiple myeloma aspirates (n=414) before treatment

2008-06-13 | E-GEOD-4581 | biostudies-arrayexpress

Transcription profiling of human plasma cell samples from multiple myeloma patients

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients. Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with high dose therapy and stem cell transplants termed Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation

2008-06-13 | E-GEOD-2658 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data