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Human induced pluripotent stem cells (iPSCs) are a promising tool to investigate pathogenic mechanisms underlying human genetic conditions, such as congenital anomalies of the kidney and urinary tract (CAKUT). Currently, iPSC-based research in pediatrics is limited by the invasiveness of cell collection.Urine cells (UCs) were isolated from pediatric urine specimens, including bag collections, and reprogrammed using episomal vectors into urinary iPSCs (UiPSCs). Following iPSC-quality assessment, human kidney organoids were generated.UCs were isolated from 71% (12/17) of single, remnant urine samples obtained in an outpatient setting (patients 1 month-17 years, volumes 10-75 ml). Three independent UCs were reprogrammed to UiPSCs with early episome loss, confirmed pluripotency and normal karyotyping. Subsequently, these UiPSCs were successfully differentiated into kidney organoids, closely resembling organoids generated from control fibroblast-derived iPSCs. Importantly, under research conditions with immediate sample processing, UC isolation was successful 100% for target pediatric CAKUT patients and controls (11/11) after at most two urine collections.Urine in small volumes or collected in bags is a reliable source for reprogrammable somatic cells that can be utilized to generate kidney organoids. This constitutes an attractive approach for patient-specific iPSC research involving infants and children with wide applicability and a low threshold for participation.

Branching morphogenesis, defined as growth and branching of epithelial tubules during embryogenesis, is a fundamental feature of renal, lung, mammary gland, submandibular gland, and pancreatic morphogenesis in mammals. Disruption of branching morphogenesis has been demonstrated to result in maldevelopment of some of these organs. Genetic studies performed in affected humans and mutant mice have implicated transcription factors, secreted growth factors, and cell surface signaling molecules as critical regulators of branching morphogenesis. These factors function within networks that appear to exert tight control over the number and location of branches. This review summarizes current knowledge regarding the molecular control of branching morphogenesis in vivo with particular emphasis on the genetic contribution to perturbed branching morphogenesis in mice and humans.

Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice.