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Abstract: TH-PO629

Developmental Trajectories Inform the Derivation of Podocytes in-a-Dish

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

  • Tran, Trinh k (tracy), 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

Group or Team Name

  • The McMahon Laboratory
Background

In the renal corpuscle, podocytes, mesangial cells and vascular endothelial cells form a highly organized filtration device that enables plasma fluid to pass from the circulatory system into the epithelail network of the nephron. The derivation of podocyte-like cells from differentiating pluripotent stem cells has been reported by a number of groups through a variety of approaches. Before moving to disease modeling and drug discovery, an evaluation of the properties of in vitro derived cells to their in vivo counterparts is important.

Methods

In this study, we used in vivo studies, single-cell RNA sequencing and bioinformatics to explore the developmental trajectory of the human podocyte. Employing a fluorescently labeled hESC line to visualize and isolate in vitro derived podocyte-like cells, we performed a comparative analysis of these cells with their human embryonic counterparts.

Results

Through high-resolution microscopy, chromatin structure profiling, single-cell and bulk transcriptional profiling, we identified transcriptional landmarks during in vivo and in vitro podocyte development.

Conclusion

We found that hESC-derived podocytes shared molecular signatures with normal human podocytes, including the ability to form intricate interactions with their neighbors and attract blood vessels. A substantial podocyte profile is generated without accompanying interactions with mesangial or endothelial cell types. Our analyses also identified distinct transcriptional signatures between in vitro and in vivo-derived cells that point to opportunities to improve podocyte production in culture.

Funding

  • NIDDK Support