Joseph V. BONVENTRE Massachusetts Institute of Technology, USA "Human ureteric bud organoids and functional collecting duct epithelial derived from pluripotent stem cells"
ABSTRACT The kidney derives from a complex interplay between the metanephric mesenchyme (MM) and ureteric bud. We have previously reported a technique to derive MM-derived kidney tissue from directed differentiation of human pluripotent stem cells (hPSCs). I will describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional collecting duct cells. The hPSCs are first induced to generate pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and distal tip localization of RET expression as is seen in normal kidney development. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into inner medullary collecting duct (CD) organoids, which contain >95% CD cell types as estimated by scRNA-seq. The CD epithelia demonstrate ENaC-mediated vectorial sodium transport and generation of a transepithelial potential by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells. Proteomic studies reveal that FOXI1 induction in principal cells is sufficient to convert them to intercalated cells.
BIO Joseph Bonventre is the Samuel A. Levine Distinguished Professor of Medicine and Constantine L. Hampers Distinguished Chair at Harvard Medical School and Professor of Health Sciences and Technology at the Massachusetts Institute of Technology. He is Chief of the Renal Division and Founding Chief of the Engineering in Medicine Division of the Brigham and Women's Hospital. In addition to his B.S. with distinction in Engineering Physics from Cornell, Dr. Bonventre holds M.D. and Ph.D. degrees in Biophysics from Harvard University. He has honorary doctorate degrees from Mt. Saint Mary’s College and from the Norwegian Institute of Science and Technology in Norway. He was Director of the Harvard-MIT Division of Health Sciences and Technology for 10 years.
Dr. Bonventre’s research focuses primarily on the study of kidney injury and repair and signal transduction, with a special emphasis on the role of inflammation, biomarkers, DNA damage and stem cells. His recent work also involves the generation of kidney organoids from stem cells and their use in kidney disease modeling. His laboratory generated a protocol for direct differentiation of human stem cells to metanephric mesenchyme kidney organoids that is widely used. He has recently generated a novel protocol for the generation of ureteric bud organoids and created functional collecting duct principal and intercalated cell lines. He discovered Kidney Injury Molecule-1 (KIM-1) which is a widely used urinary biomarker for proximal tubule injury. He has more than 415 original research publications, 150 reviews/chapters and editorials and 3 books. His work has been referenced more than 81,800 times (>28,000 since 2017) and 143 of his publications have been cited more than 143 times each (h-index). He has trained over 230 individuals in his laboratory, many of whom have assumed leadership positions in science and academic medicine. Dr. Bonventre has been elected to the American Society of Clinical Investigation (ASCI), the Association of American Physicians (AAP), the American Clinical and Climatological Association (ACCA) and the American Institute for Medical and Biological Engineering (AMBIE) and has been elected a Fellow of the American Association for the Advancement of Science. He is a member of the Executive Committee of the Harvard Stem Cell Institute (HSCI).
Dr. Bonventre is a former member of the Council and Past-President of the American Society of Nephrology and founding member of the Board of Directors of the National Space Biology Research Institute. Dr. Bonventre is Editor of Seminars in Nephrology. He has been awarded the Osler Medal of the Royal Society of Physicians and the Bywaters Award of the International Society of Nephrology and the Massry Award of the National Kidney Foundation (NKF). He has served as a member of the Council of the International Society of Nephrology and Advisory Council of the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Bonventre has co-founded and is an advisor for a number of companies.