Journal
NATURE BIOTECHNOLOGY
Volume 33, Issue 11, Pages 1193-U127Publisher
NATURE RESEARCH
DOI: 10.1038/nbt.3392
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Funding
- US National Institutes of Health (NIH) [R37 DK039773, R01 DK072381]
- Postdoctoral Fellowship for Research Abroad
- American Heart Association [11FTF7320023]
- Harvard Stem Cell Institute
- NIH [DK102826]
- National Kidney Foundation Young Investigator Grant
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Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) may enable organ regeneration, disease modeling and drug screening. We report an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2(+)SALL1(+)WT1(+)PAX2(+) NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8(+)LHX1(+) renal vesicles that self-organize into nephron structures. In both two-and three-dimensional culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.
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