Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids
Brigham and Women's Hospital · Harvard University · +7 more institutions
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…
Citation impact
- FWCI
- 25.60
- Percentile
- 100%
- References
- 54
Authors
21- BFBenjamin FreedmanCorresponding
Brigham and Women's Hospital, Harvard University, University of Washington
- CRCraig R. Brooks
Brigham and Women's Hospital, Harvard University
- AQAlbert Q. Lam
Brigham and Women's Hospital, Harvard University, Harvard Stem Cell Institute
- HFHongxia Fu
Boston Children's Hospital, Harvard University
- RMRyuji Morizane
Brigham and Women's Hospital, Harvard University
Topics & keywords
- Induced pluripotent stem cell
- Cell biology
- Biology
- Cilium
- Epiblast
- Organoid
- Kidney
- Polycystic kidney disease
Funding
- AHAmerican Heart Association
- HAHeart and Stroke Foundation of Canada
- BABrigham and Women's Hospital
- MGMassachusetts General Hospital
- UOUniversity of Washington
- SCSeattle Children's Research Institute
- UOUniversity of British Columbia
- NINational Institutes of HealthAwards: DK099532, DK102826, DK39773, DK51050
- HSHarvard Stem Cell Institute
- JSJapan Society for the Promotion of ScienceAward: 84545
- NCNational Center for Advancing Translational Sciences