The Genito-Urinary Developmental Molecular Anatomy Project (GUDMAP) has generated information and research tools to enhance our understanding of the development of urogenital system, both informing and stimulating research into urogenital development, and associated disorders and disease. Our proposed studies focus on the developing kidney complementing existing data available through the GUDMAP website. The functional unit of the kidney is the nephron ? hence, our focus on obtaining a thorough understanding of mammalian nephrogenesis. The current GUDMAP view of this process is largely two-dimensional and mouse focused. We will harness recent advances in both static and live dynamic cell imaging, the access to human kidney specimens and the development of pluripotent stem cell (PSC) culture-seeded nephrogenesis to extend our understanding of both mouse and human nephrogenesis.
In Aim 1, we will develop high-resolution 3D views of mouse and human nephrogenesis through selective imaging approaches comparing mouse and human nephrogenesis to develop comparative 3D molecular atlases of nephron patterning and nephron morphogenesis.
In Aim 2, we will take advantage of improvements in imaging and organ culture, and a bank of genetically modified mouse strains, to perform time lapse imaging of the nephron progenitor niche, and the formation, morphogenesis and patterning of the mouse nephron. Dynamic imaging studies will be applied to pluripotent stem cell (PSC)-derived models of human nephrogenesis. Together, these studies will significantly enrich the GUDMAP resource generating comparative 4D views of nephron development in the mouse and human kidney. Given the recent advances in the directed differentiation of PSCs into nephron-like structures, the studies will provide a benchmark for normal nephrogenesis that will guide the emerging field of regenerative kidney biology.
Regenerative approaches to treat kidney disease are predicated on a good understanding of the developmental mechanisms that build a functional kidney. The proposal sets out to develop comparative, views of the nephron forming processes in space and over time in the mouse and human kidney. These studies will provide an important resource for kidney researchers and a benchmark for efforts to engineer functional kidney structures.
| Lindström, Nils O; Guo, Jinjin; Kim, Albert D et al. (2018) Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney. J Am Soc Nephrol 29:806-824 |
| Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy et al. (2018) Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis. Dev Cell 45:651-660.e4 |
| Lindström, Nils O; McMahon, Jill A; Guo, Jinjin et al. (2018) Conserved and Divergent Features of Human and Mouse Kidney Organogenesis. J Am Soc Nephrol 29:785-805 |
| Ryan, Danica; Sutherland, Megan R; Flores, Tracey J et al. (2018) Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants. EBioMedicine 27:275-283 |
| Lindström, Nils O; Tran, Tracy; Guo, Jinjin et al. (2018) Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning. J Am Soc Nephrol 29:825-840 |
