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Multiphoton imaging bolsters findings on in vitro differentiation of pluripotent stem cell-derived podocyte

The renal corpuscle of the kidney comprises a glomerular vasculature embraced by podocytes and supported by mesangial myofibroblasts. Their combined actions are essential for the formation of an acellular plasma filtrate that passes through the podocyte-generated slit diaphragm into the nephron. Mutations in podocyte-expressed genes lead to chronic disease. An enhanced understanding of podocyte development and function to create biologically relevant in vitro podocyte models is a clinical imperative. Our team studied human podocyte development using scRNA-seq technology and established a framework to unbiasedly evaluate human embryonic stem cells (hESC)-derived podocytes. Confocal imaging served as a powerful tool for us to capture compelling immunofluorescent and fluorescent in situ hybridization validations of transcriptomic findings. Additionally, we utilized intravital multiphoton confocal microscopy in collaboration with the Peti-Peterdi laboratory to capture live hESC-derived podocytes recruiting the host vasculature upon transplantation under the mouse kidney capsule. Our studies show similarities between hESC-derived podocytes and human podocytes that suggest an intrinsic regulatory program of podocyte development though transplant studies indicate vascular interactions refine and improve the mature podocyte state. These studies support the application of hESC-derived podocytes to model disease and to restore or replace normal kidney functions.

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Tran T, Lindström NO, Ransick A, De Sena Brandine G, Guo Q, Kim AD, Der B, Peti-Peterdi J, Smith AD, Thornton M, Grubbs B, McMahon JA, McMahon AP:
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.

Dev Cell. 2019 Jul 1;50(1):102-116.e6. doi: 10.1016/j.devcel.2019.06.001.