{"id":"doi:10.1038/ncomms9715","kind":"article","title":"Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids","authors":["Benjamin Freedman","Craig R. Brooks","Albert Q. Lam","Hongxia Fu","Ryuji Morizane","Vishesh Agrawal","Abdelaziz F. Saad","Michelle K. Li","Michael R. Hughes","Ryan Vander Werff","Derek Peters","Junjie Lu","Anna E. Eastman","Andrew M. Siedlecki","M. Todd Valerius","Kiran Musunuru","Kelly Marshall McNagny","Theodore I. Steinman","Jing Zhou","Paul H. Lerou","Joseph Vincent Bonventre"],"author_count":21,"year":2015,"published":"2015-10-23","venue":"Nature Communications","cited_by":784,"doi":"10.1038/ncomms9715","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/ncomms9715","archive_url":"https://space-kitty.com/papers/doi:10.1038/ncomms9715","updated":null,"pmid":"26493500","pmcid":null,"openalex_id":"W2176166968","pdf_url":"https://www.nature.com/articles/ncomms9715.pdf","abstract":"Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Pluripotent Stem Cells Research"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids\" by Benjamin Freedman, Craig R. Brooks, Albert Q. Lam et al., https://doi.org/10.1038/ncomms9715, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"organoids","name":"Organoids & Organ-on-Chip","domain_slug":"biotech"}],"cited_in_dossiers":[]}