TY - JOUR T1 - Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships JF - bioRxiv DO - 10.1101/432161 SP - 432161 AU - Sara E Howden AU - Jessica M Vanslambrouck AU - Sean B Wilson AU - Ker Sin Tan AU - Melissa H Little Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/10/01/432161.abstract N2 - While mammalian kidney morphogenesis has been well documented, human kidney development is poorly understood. Here we combine reprogramming, CRISPR/Cas9 gene-editing and organoid technologies to study human nephron lineage relationships in vitro. Early kidney organoids contained a SIX2+ population with a transcriptional profile akin to human nephron progenitors. Lineage-tracing using gene-edited induced pluripotent stem cell (iPSC) lines revealed that SIX2-expressing cells contribute to nephron formation but not to the putative collecting duct epithelium. However, Cre-mediated temporal induction of the SIX2+ lineage revealed a declining capacity for these cells to contribute to nephron formation over time. This suggests human kidney organoids, unlike the developing kidney in vivo, lack a nephron progenitor niche capable of both self-renewal and ongoing nephrogenesis. Nonetheless, human iPSC-derived kidney tissue maintains previously identified lineage relationships supporting the utility of pluripotent stem cell-derived kidney organoids for interrogating the molecular and cellular basis of early human development. ER -