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Human kidney organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease and regeneration, present an opportunity to explore the transcriptional plasticity of podocytes. Here, transcriptional profiling of more than 12,000 single cells from human PSC\u2013derived kidney organoid cultures was used to identify robust and reproducible cell lineage gene expression signatures shared with developing human kidneys based on trajectory analysis. Surprisingly, the gene expression signature characteristic of developing glomerular epithelial cells was also observed in glomerular tissue from a kidney disease cohort. This signature correlated with proteinuria and inverse eGFR, and it was confirmed in an independent podocytopathy cohort. Three genes in particular were further characterized as potentially novel components of the glomerular disease signature. We conclude that cells in human PSC\u2013derived kidney organoids reliably recapitulate the developmental transcriptional program of podocytes and other cell lineages in the human kidney and that transcriptional profiles seen in developing podocytes are reactivated in glomerular disease. Our findings demonstrate an approach to identifying potentially novel molecular programs involved in the pathogenesis of glomerulopathies.<\/jats:p>","DOI":"10.1172\/jci.insight.122697","type":"journal-article","created":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T09:16:22Z","timestamp":1547111782000},"source":"Crossref","is-referenced-by-count":92,"title":["Organoid single cell profiling identifies a transcriptional signature of glomerular disease"],"prefix":"10.1172","volume":"4","author":[{"given":"Jennifer L.","family":"Harder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasree","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, 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