Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter
Albert D. Kim,
Blue B. Lake,
Song Chen,
Yan Wu,
Jinjin Guo,
Riana K. Parvez,
Tracy Tran,
Matthew E. Thornton,
Brendan Grubbs,
Jill A. McMahon,
Kun Zhang,
Andrew P. McMahon
Affiliations
Albert D. Kim
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Blue B. Lake
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Song Chen
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Yan Wu
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Jinjin Guo
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Riana K. Parvez
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Tracy Tran
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Matthew E. Thornton
Maternal Fetal Medicine Division, University of Southern California, Los Angeles, CA, USA
Brendan Grubbs
Maternal Fetal Medicine Division, University of Southern California, Los Angeles, CA, USA
Jill A. McMahon
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Kun Zhang
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA; Corresponding author
Andrew P. McMahon
Department of Stem Cell Biology and Regenerative Medicine, Broad-CIRM Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Corresponding author
Summary: Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney's filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types. : Biological Sciences; Cell Biology; Developmental Biology; Omics Subject Areas: Biological Sciences, Cell Biology, Developmental Biology, Omics
