Project description:Localization of Fusobacterium nucleatum in the placenta may be associated with pregnancy complications including preeclampsia (PE), but its specific pathobiology is unknown. Our aim was to analyze the effect of Fusobacterium nucleatum on HUVEC cells to further elucidate placental dysfunction in the context of Fusobacterium nucleatum infestation.
Project description:Question Addresses: What is the gene expression profile from human umbilical vein endothelial cells (HUVEC) and human Jurkat T cells after irradiation (IR)? What, if any, is the effect of co-culturing these two cell types on gene expression? There are eight experimental conditions for this experiment: (1) non-irradiated HUVEC; (2) irradiated HUVEC; (3) non-irradiated Jurkat; (4) irradiated Jurkat; (5) non-irradiated HUVEC + non-irradiated Jurkat+; (6) non-irradiated HUVEC + irradiated Jurkat; (7) irradiated HUVEC + non-irradiated Jurkat; (8) irradiated HUVEC + irradiated Jurkat. A common, pooled reference consisting of RNA taken from conditions 1-8 as described above was used for all hybridizations.
Project description:Platelet-rich plasma (PRP), which is prepared by concentrating platelets in autologous blood, shows efficacy in chronic skin wounds via multiple growth factors. However, it exhibits heterogeneity across patients, leading to unstable therapeutic efficacy. Human induced pluripotent stem cell-derived megakaryocytes and platelets (iMPs) are capable of providing a stable supply, holding promise as materials for novel therapies. Thus, we evaluated the effect of iMPs on wound healing in vitro. iMPs specifically released FGF2 and exhibited superior enhancement on HUVEC proliferation compared to PRP. RNA-seq revealed that iMPs induce polarization to stalk cells and enhance ANGPTL4 gene expression in HUVECs. These mechanisms were suggested to provide the superior effects of iMPs.
Project description:Cancer cells evade T-cell-mediated killing through poorly understood mechanisms of tumour–immune interactions. Dendritic cells (DCs), especially type-1 conventional DCs (cDC1), mediate T-cell priming and therapeutic efficacy against tumours. Besides pattern recognition receptors (PRRs), how DC functions are shaped by other environmental cues remains incompletely defined. Nutrients are emerging mediators of adaptive immunity, but whether nutrients impact DC function or innate–adaptive cell communication is largely unresolved. Here, we establish glutamine as an intercellular metabolic checkpoint to mediate tumour–cDC1 crosstalk and license cDC1 functionality for activating cytotoxic T cells. Intratumoral glutamine supplementation inhibits tumour growth by augmenting cDC1-mediated CD8+ T-cell immunity, and also overcomes therapeutic resistance to checkpoint blockade and T-cell-mediated immunotherapies. Mechanistically, tumour cells and cDC1 compete for glutamine uptake via transporter SLC38A2 to tune anti-tumour immunity. Nutrient screening and integrative analyses show that glutamine is the dominant amino acid for promoting cDC1 function, by signalling via FLCN to impinge upon TFEB function. Loss of FLCN in DCs selectively impairs cDC1 function in vivo in a TFEB-dependent manner, and phenocopies SLC38A2 deficiency by abrogating anti-tumour therapeutic effect of glutamine supplementation. Our findings establish glutamine-mediated intercellular metabolic crosstalk between tumour cells and cDC1 that underpins tumour immunoevasion, and reveal glutamine acquisition and signalling in cDC1 as limiting events for DC activation and putative targets for cancer treatment.