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Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships

Sara E Howden, Jessica M Vanslambrouck, Sean B Wilson, Ker Sin Tan, Melissa H Little
doi: https://doi.org/10.1101/432161
Sara E Howden
1Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia
2Department of Paediatrics, The University of Melbourne, VIC, Australia
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  • For correspondence: melissa.little@mcri.edu.au sara.howden@mcri.edu.au
Jessica M Vanslambrouck
1Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia
2Department of Paediatrics, The University of Melbourne, VIC, Australia
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Sean B Wilson
1Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia
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Ker Sin Tan
1Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia
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Melissa H Little
1Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia
2Department of Paediatrics, The University of Melbourne, VIC, Australia
3Department of Anatomy and Neuroscience, The University of Melbourne, VIC, Australia
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  • For correspondence: melissa.little@mcri.edu.au sara.howden@mcri.edu.au
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 01, 2018.
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Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships
Sara E Howden, Jessica M Vanslambrouck, Sean B Wilson, Ker Sin Tan, Melissa H Little
bioRxiv 432161; doi: https://doi.org/10.1101/432161
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Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships
Sara E Howden, Jessica M Vanslambrouck, Sean B Wilson, Ker Sin Tan, Melissa H Little
bioRxiv 432161; doi: https://doi.org/10.1101/432161

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