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Abstract: FR-OR18

A Single-Cell Atlas of Human Fetal Kidneys Identifies Cell States Associated with Rare and Common Human Disease

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Levinsohn, Jonathan, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Kloetzer, Konstantin A., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Sasaki, Kotaro, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Background

Abnormal kidney development can present as congenital anomalies which can severely impact renal function. It is further thought that development may also influence more subtle phenotypes that can present later in life. Low birth weight is a risk factor for hypertension and prematurity is a risk factor for CKD.

Methods

We performed single cell RNA sequencing of 5 human fetal kidneys. We mapped developmental trajectories using RNA velocity and CellRank, creating a probabilistic model for cell differentiation in nephron development.

Results

We created an atlas of cells of human fetal kidney with a total of 65,348 cells, the largest, most comprehensive atlas of this tissue to date. This atlas demonstrates contiguous trajectories of cell states starting from a putative progenitor population to mature cell types. By examining diffusive properties within this map, we were able to identify and map previously hypothesized transitions between PTs, PECs and podocytes. We also applied this model to identify the cell states and transitions during fetal development to both common and rare human genetic disease, finding cell states that appear to be important in CAKUT, as well as cell states that influence adult eGFR.

Conclusion

We present the most complete atlas of the human fetal kidney to date. Using this atlas, we identify cell states are associated with human genetic disease and that these states are correlated by phenotype, leading to novel insights into developmental mechanisms of human disease.

Funding

  • NIDDK Support