Abstract: FR-PO941
Single-Nucleus Transcriptome Sequencing of Fetal Kidney Cells Identifies a Transient Pro-Angiogenic Signature in Developing Podocytes
Session Information
- Development, Stem Cells, Regenerative Medicine - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 501 Development, Stem Cells, and Regenerative Medicine: Basic
Authors
- Kim, Albert D., Keck School of Medicine of the University of Southern California, Los Angeles, California, United States
- McMahon, Andrew P., Keck School of Medicine of the University of Southern California, Los Angeles, California, United States
- Zhang, Kun, University of California at San Diego, San Diego, California, United States
Group or Team Name
- McMahon Laboratory
Background
The renal corpuscle is composed of cell types including parietal epithelium, podocytes, mesangium, and endothelium. How this critical structure is generated from its constituent precursor cells during development is not well understood. Transcriptional profiling of the developing human kidney can provide novel insights into developmental processes.
Methods
Nephrogenic zone and renal corpuscles from 13 to 16 week human fetal kidneys were profiled by single nuclear Drop-seq and cell clusters were resolved using Pagoda2. To better understand nephron development, we performed trajectory analysis using Monocle. Specific predictions of genes identifying specific cell types and developmental transition were validated by in situ hybridization and immunohistochemistry. A specific hypothesis formulated on the transient production of secreted factors by podocytes co-regulating vascular and mesangial cell types was explored in vitro.
Results
SnDrop-seq identified 12 different nephrogenic clusters that were identified by known markers. Novel gene expression was discovered and validated in our analysis. Computational ordering of transcriptomes along a developmental trajectory revealed that a novel transient expression signature was present within precursors progressing to the podocyte lineage prior to expression of mature markers. Anatomical and in vitro characterization of these genes support an angiogenesis-promoting function within this transient population.
Conclusion
Previous studies have established that cell signaling including VEGF signaling is required for glomerular vascularization in vivo, however attempts to recapitulate this process in vitro have failed. Our findings provide insight into a critical spatiotemporal program that aids in the formation of the primary filtration unit in the kidney. Our findings provide new insight into human glomerular developmental programs and highlight novel targets-of-interest to explore in human kidney disease.
Funding
- NIDDK Support