Origin of parietal podocytes in atubular glomeruli mapped by lineage tracing

Schulte, Kevin; Arkill, Kenton; Berger, Katja; Boor, Peter; Jirak, Peggy; Gelman, Irwin; Neal, Christopher; Kriz, Wilhelm; Floege, J�rgen; Smeets, Bart; Moeller, Marcus J.

Abstract

Parietal podocytes are fully differentiated podocytes lining Bowman's capsule where normally only parietal epithelial cells (PECs) are found. Parietal podocytes formthroughout life and are regularly observed in human biopsies, particularly in atubular glomeruli of diseased kidneys; however, the origin of parietal podocytes is unresolved. To assess the capacity of PECs to transdifferentiate into parietal podocytes, we developed and characterized a novelmethod for creating atubular glomeruli by electrocoagulation of the renal cortex in mice. Electrocoagulation produced multiple atubular glomeruli containing PECs as well as parietal podocytes that projected from the vascular pole and lined Bowman's capsule. Notably, induction of cell death was evident in some PECs. In contrast, Bowman's capsules of control animals and normal glomeruli of electrocoagulated kidneys rarely contained podocytes. PECs and podocytes were traced by inducible and irreversible genetic tagging using triple transgenic mice (PEC- or Pod-rtTA/LC1/R26R). Examination of serial cryosections indicated that visceral podocytes migrated onto Bowman's capsule via the vascular stalk; direct transdifferentiation from PECs to podocytes was not observed. Similar results were obtained in a unilateral ureter obstruction model and in human diseased kidney biopsies, in which overlap of PEC- or podocyte-specific antibody staining indicative of gradual differentiation did not occur. These results suggest that induction of atubular glomeruli leads to ablation of PECs and subsequent migration of visceral podocytes onto Bowman's capsule, rather than transdifferentiation from PECs to parietal podocytes. Copyright © 2014 by the American Society of Nephrology.

Citation

Schulte, K., Arkill, K., Berger, K., Boor, P., Jirak, P., Gelman, I., …Moeller, M. J. (2014). Origin of parietal podocytes in atubular glomeruli mapped by lineage tracing. Journal of the American Society of Nephrology, 25(1), 129-141. https://doi.org/10.1681/ASN.2013040376

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2013
• Online Publication Date: Dec 31, 2013
• Publication Date: 2014-01
• Deposit Date: Aug 28, 2018
• Journal: Journal of the American Society of Nephrology
• Print ISSN: 1046-6673
• Electronic ISSN: 1533-3450
• Publisher: American Society of Nephrology
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 1
• Pages: 129-141
• DOI: https://doi.org/10.1681/ASN.2013040376
• Keywords: Nephrology; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1104962
• Publisher URL: https://jasn.asnjournals.org/content/25/1/129
• PMID: 00032915