Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells

Erythropoietin (EPO) is a crucial hormone for erythropoiesis and produced by adult kidneys. Insufficient EPO production in chronic kidney disease (CKD) can cause renal anemia. Although hypoxia-inducible factors (HIFs) are known as a main regulator, the mechanisms of EPO production have not been fully elucidated. In this study, we aimed to examine the roles of retinoic acid (RA) in EPO production using EPO-producing cells derived from human induced pluripotent stem cells (hiPSC-EPO cells) that we previously established. RA augmented EPO production by hiPSC-EPO cells under hypoxia or by treatment with prolyl hydroxylase domain-containing protein (PHD) inhibitors that upregulate HIF signals. Combination treatment with RA and a PHD inhibitor improved renal anemia in vitamin A-depleted CKD model mice. Our findings using hiPSC-EPO cells and CKD model mice may contribute to clarifying the EPO production mechanism and developing efficient therapies for renal anemia

Differentiation and isolation of iPSC-derived remodeling ductal plate-like cells by use of an AQP1-GFP reporter human iPSC line

Cholangiocytes are the epithelial cells that line bile ducts, and ductal plate malformation is a developmental anomaly of bile ducts that causes severe congenital biliary disorders. However, because of a lack of specific marker genes, methods for the stepwise differentiation and isolation of human induced pluripotent stem cell (hiPSC)-derived cholangiocyte progenitors at ductal plate stages have not been established. We herein generated an AQP1-GFP reporter hiPSC line and developed a combination treatment with transforming growth factor (TGF) β2 and epidermal growth factor (EGF) to induce hiPSC-derived hepatoblasts into AQP1⁺ cells in vitro. By confirming that the isolated AQP1⁺ cells showed similar gene expression patterns to cholangiocyte progenitors at the remodeling ductal plate stage around gestational week (GW) 20, we established a differentiation protocol from hiPSCs through SOX9⁺CK19⁺AQP1⁺ remodeling ductal plate-like cells. We further generated 3D bile duct-like structures from the induced ductal plate-like cells. These results suggest that AQP1 is a useful marker for the generation of remodeling ductal plate cells from hiPSCs. Our methods may contribute to elucidating the differentiation mechanisms of ductal plate cells and the pathogenesis of ductal plate malformation

Electronics for HARPO: Design, development and validation of electronics for a high performance polarised-Gamma-ray detector

International audienceWe designed and built an experimental apparatus based on a time projection chamber, a novel scheme for high performance γ-ray astronomy and polarimetry in the γ → e+e- regime. This presentation focuses on the electronics aspect of the detector and, in particular, on the versatile dedicated trigger system that we have developed which allowed us to take data on beam with a high γ-conversion signal efficiency and a high rejection factor for single tracks and upstream conversion background events. Our scheme allows for the selective collection of γ conversions in a high-background-rate environment, such as that which is present in orbit, with a fine 3D imaging of the events and very low (in particular electronics) background, at a mild cost in terms of the number of electronics channels and therefore of electrical power consumption