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RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

ABSTRACT: RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

PROVIDER: PRJNA588261 | ENA |

REPOSITORIES: ENA

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RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

Project description:Altered bone marrow hematopoiesis and immune suppression is a hallmark of myelodysplastic syndrome (MDS). While the bone marrow microenvironment influences malignant hematopoiesis, the mechanism leading to MDS-associated immune suppression is unknown. We tested whether mesenchymal stromal cells (MSCs) contribute to this process. Here, we developed a model to study cultured MSCs from MDS patients compared to similar aged matched normal controls for regulation of immune function. MSCs from MDS patients (MDS-MSC) and healthy donor MSC (HD-MSC) exhibited a similar in vitro phenotype and neither had a direct effect on NK cell function. However, when MDS and HD-MSCs were cultured with monocytes, only the MDS-MSCs acquired phenotypic and metabolic properties of myeloid-derived suppressor cells (MDSCs), with resulting suppression of NK cell function, along with T cell proliferation. A unique MSC transcriptome was observed in MDS-MSCs compared to HD-MSCs, including increased expression of the reactive oxygen species (ROS) regulator, ENC1. High ENC1 expression in MDS-MSC induced suppressive monocytes with increased INHBA, a gene that encodes for a member of the TGF? superfamily of proteins. These monocytes also had reduced expression of the TGF? transcriptional repressor MAB21L2, further adding to their immune suppressive function. Silencing ENC1 or inhibiting ROS production in MDS-MSCs abrogated the suppressive function of MDS-MSC conditioned monocytes. In addition, silencing MAB21L2 in healthy MSC conditioned monocytes mimicked the MDS-MSC suppressive transformation of monocytes. Our data demonstrate that MDS-MSCs are responsible for inducing an immune suppressive microenvironment in MDS through an indirect mechanism involving monocytes.

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Expression data of 4T1 mammary cancer cells cultured in MSC-conditioned medium or co-cultured with MSCs

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Effect of tumor conditioned medium of human mesenchymal stem cell (MSCs)

Project description:We have employed whole genome microarray to identify changes in gene expression in human MSCs exposed to tumor conditioned medium Human MSC line (hMSC-TERT) was exposed to tumor conditioned medium (CM) from FaDu hypo pharyngeal cancer cell line for 7 day. Subsequently, RNA was extracted using Roche MagNA Pure automated nucleic acid purification system. Control RNA was collected from the same batch of MSCs exposed to normal medium. Extracted RNA was labeled and then hybridized to the one-color Agilent Human GE 4x44K v2 Microarray chip.

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Murine MSCs: MSC-exosome-hypoxia vs MSC-exosome-normoxia

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miRNA expression profiles of EVs from control and MDS mice

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