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Expression data from cultured mouse bone-marrow monocytes.

ABSTRACT: Expression data from cultured mouse bone-marrow monocytes.

PROVIDER: PRJNA604192 | ENA |

REPOSITORIES: ENA

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Expression data from cultured mouse bone-marrow monocytes.

Project description:Retinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in mouse monocytes. The immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy. Within solid tumors, why monocytes preferentially differentiate into immunosuppressive tumor associated macrophages (TAMs) but not immunostimulatory dendritic cells (DCs) remains unclear. Using multiple murine sarcoma models, we found that the TME induced retinoic acid (RA) production by tumor cells, which polarized intratumoral monocyte differentiation towards TAMs and away from DCs via suppression of DC-promoting transcription factor Irf4. Genetic inhibition of RA production by tumor cells or pharmacologic inhibition of RA signaling within TME increased stimulatory monocyte-derived cells, enhanced T cell-dependent anti-tumor immunity and demonstrated striking synergy with immune checkpoint blockade. Further, RA responsive gene signature in human monocytes correlated with an immunosuppressive TME in multiple human tumors. RA has been long considered as an anti-cancer agent, but our work demonstrates its tumorigenic capability via myeloid-mediated immune suppression and provides proof of concept for targeting this pathway for tumor immunotherapy.

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Transcriptional characteristics of human primary, bone marrow-derived and iPSC-derived monocytes and macrophages [RNA-Seq]

Project description:In vitro models to study diseases often involve human primary monocytes which are subjected to a interpersonal variability and short half-life. Bone marrow and iPSC-derived monocytes as an alternative for these in vitro models. However, the similarities and differences of these cells compared to human circulating monocytes has not yet been described. In this study, we compared human primary circulating, bone marrow-derived and iPSC-derived monocytes and macrophages and its functional, epigenomic, transcriptomic and morpholoigcal lanscape.

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Bone marrow microenvironment: interaction of monocytes and stromal cells

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