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Expression profiling in exosomal miRNAs of human bone marrow stromal cells derived from multiple myeloma patients

ABSTRACT: Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110271 | GEO | 2018/06/08

REPOSITORIES: GEO

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The gene expression profiles of human bone marrow stromal cells derived from multiple myeloma patients

Project description:Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Multiple myeloma (MM) is refractory hematologic malignancy. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that exosome-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the exosomes and exosomal miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread.

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Expression profiling in cellular miRNAs of human bone marrow stromal cells derived from multiple myeloma patients

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Expression profiling in exosomal miRNAs secreted from human bone marrow stromal cells

Project description:The aging of bone marrow stromal cells (BMSCs) lead to decreased ability to maintain hematopoiesis, however, effects of aging on BMSC-derived exosomes in bone marrow microenvironment remain unclear. The aim of this study is therefore to determine the age-related change of BMSC-derived exosomal miRNAs. Human BMSCs of young (yBMSC s, age of donors: 19 and 20 years) and elderly (eBMSC s, age of donors: 68 and 72 years) donors were purchased from Lonza. BM samples were obtained from MM patients (age of donors: 62 and 77 years) in accordance with the Declaration of Helsinki and using protocols approved by the research Ethics Committee of Tokyo Medical University (IRB No. 2648), and BMSCs derived from MM patients (mmBMSCs) were isolated using the classical plastic adhesion method. The exosomes from culture medium of BM-MSCs were isolated by Total Exosome Isolation Reagent (Invitrogen). Exosomal miRNA profiling was done using a TaqMan low-density array (ABI), and Studentâ??s t-test was used to determine statistical significance for comparisons between young and old groups using R software.

2017-05-12 | E-GEOD-78865 | biostudies-arrayexpress

Expression profiling in exosomal miRNAs secreted from human bone marrow stromal cells

2017-05-12 | GSE78865 | GEO

The gene expression profiles of human multiple myeloma cell lines transfected with miR-10a mimic

Project description:In multiple myeloma (MM), abnormal plasma cells interact with bone marrow (BM) stromal cells and vascular cells among others. Bone marrow stromal cells (BMSCs) interact with MM cells in the bone marrow (BM), and also create a permissive microenvironment for MM cell growth and survival. Recent evidence indicated that extracellular vesicles (EVs)-mediated MM cell-BMSC communication plays an important role in the MM microenvironment. In this study, we investigated the biological property of the EVs and EV-miRNAs derived from BMSCs, aiming to establish the emerging strategies to target MM microenvironment to prevent tumor growth and spread. We found that the MM-BMSC-EVs enhanced the cell proliferation of RPMI8226. The EV-miRNA expression was different between MM-BMSCs and Normal-BMSCs, and some miRNAs, including miR-10a, were significantly up-regulated in the MM-BMSC-EVs. We then visualized with an in vitro model the uptake of Cy3-labeled miR-10a into RPMI8226 via EVs. To identify the function of miR-10a in MM cells, miR-10a mimic was transfected into RPMI8226 cells.

2018-09-30 | GSE118282 | GEO

Differential expression of bone marrow derived mesenchymal stem cells in patients with multiple myeloma

Project description:Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs).

2022-03-23 | GSE196321 | GEO

Expression profiling in exosomal miRNAs of human bone marrow stromal cells derived from myelodysplastic syndrome patients

Project description:Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological disorders characterized by the presence of peripheral cytopenias and an increased risk of transformation into acute myeloblastic leukemia (AML). These hematological disorders are complex and their origin in a clonal hematopoietic stem cell disorder is accepted. In the last few years, the importance of the bone marrow (BM) microenvironment has been highlighted. Bone marrow stromal cells (BMSCs) are a non-hematopoietic BM cell population considered to be the osteoblastic progenitors and a key component of the hematopoietic microenvironment. As usual, it was considered that intercellular communication could be achieved by direct cell-to-cell contact or the exchange of soluble factors and intercellular adhesion molecule. Recently, a new mechanism of intercellular communication based on the secretion of extracellular esicles (EVs) has been described. Such a mechanism modifies the functional properties of recipient cells by the transfer of bioactive molecules such as mRNA, proteins and micro-RNAs, among others. BMSCs play an important role in bone marrow environment. Recent evidences suggest that EVs act as a mediator of cell-cell interaction in hematologic neoplasms. To clarify the possible association between the cargo of BMSC-EVs and disease severity, we performed miRNA profiling in BMSC-EVs derived from MDS patients.

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Primary bone marrow stromal cells in plasma cell disorders

Project description:Multiple myeloma (MM) and its premalignant precursor MGUS (monoclonal gammopathy of undetermined significance) are clonal plasma cell diseases that develop in the bone marrow (BM) and are dependent on microenvironmental interactions. Primary bone marrow stromal cells (BMSCs) are key players in the BM microenvironment, however, their role in MGUS/MM pathophysiology is not known. We therefore investigated potential disease-specific alterations in prospectively isolated BMSCs from MM, MGUS and healthy controls. Clear disease-related BMSC surface marker and gene expression differences were recorded, and deep sequencing identified shared MGUS/MM as well as MM-specific molecular signatures. Moreover, we identified genes that were deregulated in a disease-stage manner, thus reflecting the progression from normal to MGUS and MM. Analysis of primary BMSCs revealed disease-stage related protein and gene expression patterns, which provides novel insight into the stromal transitions and their functional implications for plasma cell disease development and progression.

2024-01-31 | GSE129801 | GEO

EGR1 regulation in human bone marrow stromal cells

Project description:Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.

2019-06-27 | PXD011767 | Pride

Bone Marrow Stroma-induced Transcriptome and Regulome Signatures of Multiple Myeloma [RNA-seq]

Project description:Multiple myeloma (MM) is a hematological cancer with inevitable drug resistance. MM cells interacting with bone marrow stromal cells (BMSCs) undergo substantial changes in transcriptome and develop de novo drug resistance. As a critical component in transcriptional regulation, how chromatin landscape is transformed in MM cells and regulates the transcriptional response to BMSCs remains elusive. We profiled transcriptome and regulome for MM cells using a transwell coculture system with BMSCs. The transcriptome and regulome of MM cells from the upper transwell resembled MM cells coexisting with BMSCs from the lower chamber but were distinctive to monoculture. BMSC-induced genes were enriched in JAK2/STAT3 signaling pathway, unfolded protein stress, signatures of early plasma cells, and response to proteasome inhibitors. Genes with accessibility increased at multiple regulatory sites were preferentially induced by BMSCs and enriched in response to drug and unfavorable prognostic markers from several MM patient cohorts. We proposed JUNB and ATF4::CEBPβ as candidate transcription factors (TFs) that modulated the BMSC-induced transformation of regulome linked to the response to external stimuli. Together, we characterized BMSC-induced transcriptome and regulome signatures of MM cells and prioritized TFs for future study to depict epigenetic mechanisms of BMSC-induced drug resistance in MM.

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