Dual lineage tracing shows that glomerular parietal epithelial cells can
transdifferentiate toward the adult podocyte fate.
Authors Kaverina NV, Eng DG, Freedman BS, Kutz JN, Chozinski TJ, Vaughan JC, Miner JH,
Pippin JW, Shankland SJ
Submitted By Joshua Vaughan on 12/1/2019
Status Published
Journal Kidney international
Year 2019
Date Published 9/1/2019
Volume : Pages 96 : 597 - 611
PubMed Reference 31200942
Abstract Podocytes are differentiated post-mitotic cells that cannot replace themselves
after injury. Glomerular parietal epithelial cells are proposed to be podocyte
progenitors. To test whether a subset of parietal epithelial cells
transdifferentiate to a podocyte fate, dual reporter
PEC-rtTA|LC1|tdTomato|Nphs1-FLPo|FRT-EGFP mice, named PEC-PODO, were generated.
Doxycycline administration permanently labeled parietal epithelial cells with
tdTomato reporter (red), and upon doxycycline removal, the parietal epithelial
cells (PECs) cannot label further. Despite the presence or absence of
doxycycline, podocytes cannot label with tdTomato, but are constitutively
labeled with an enhanced green fluorescent protein (EGFP) reporter (green). Only
activation of the Nphs1-FLPo transgene by labeled parietal epithelial cells can
generate a yellow color. At day 28 of experimental focal segmental
glomerulosclerosis, podocyte density was 20% lower in 20% of glomeruli. At day
56 of experimental focal segmental glomerulosclerosis, podocyte density was 18%
lower in 17% of glomeruli. TdTomato+ parietal epithelial cells were restricted
to Bowman's capsule in healthy mice. However, by days 28 and 56 of experimental
disease, two-thirds of tdTomato+ parietal epithelial cells within glomerular
tufts were yellow in color. These cells co-expressed the podocyte markers
podocin, nephrin, p57 and VEGF164, but not markers of endothelial (ERG) or
mesangial (Perlecan) cells. Expansion microscopy showed primary, secondary and
minor processes in tdTomato+EGFP+ cells in glomerular tufts. Thus, our studies
provide strong evidence that parietal epithelial cells serve as a source of new
podocytes in adult mice.

Investigators with authorship
Joshua VaughanUniversity of Washington