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. 2022 Feb 24;10:838272. doi: 10.3389/fcell.2022.838272

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Copyright © 2022 Ravaglia, Melica, Angelotti, De Chiara, Romagnani and Lasagni.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Progenitor cells generate novel podocytes during postnatal kidney growth. (A) The kidney is composed of functional units, nephrons, each of which is made of a glomerulus and a tubule. The glomerulus is composed of a tuft of capillaries covered by visceral epithelial cells, the podocytes, and surrounded by the Bowman capsule lined on the inner surface by flat epithelial cells, parietal epithelial cells (PEC). A subpopulation of PEC localized at the urinary pole is endowed with progenitor characteristics and progressively differentiate into podocytes toward the vascular pole of the glomerulus. This occurs as the kidney grows, during childhood and adolescence in mouse models and in humans. In (B,C) representative glomeruli from transgenic Pax2.rtTA;TetO.Cre;R26.Confetti mice, an established mouse model of renal progenitor cell lineage tracing. In this model, green, yellow, cyan or red fluorescent protein is randomly expressed by Pax2- expressing cells. Pax2 is expressed by PEC progenitor cells during kidney development but is lost upon their differentiation into mature podocytes in the post-natal kidney (magnification 63x). In (B) a representative glomerulus of Pax2.rtTA;TetO.Cre;R26.Confetti mouse, induced at postnatal day P5 (when the generation of new glomeruli from the metanephric mesenchyme has already ended) for 10 days and tracked until 5 weeks of age. Fluorescent Pax2+ cells are present in the parietal epithelium of the Bowman capsule as well as inside the glomerulus. These intraglomerular Pax2-derived cells expressed synaptopodin (cyan), demonstrating their podocyte nature. In (C) a representative glomerulus of a Pax2.rtTA;TetO.Cre;R26.Confetti adult mouse induced at 5 weeks of age for 10 days, showing Pax2+ cells only in Bowman capsule. Podocytes are not labeled. (D,E) In humans, the observation that the number of podocytes increases during glomerular growth and maturation in the early years after birth, suggest the involvement of a podocyte progenitor pool during postnatal kidney growth. In D a glomerulus of a 4 years old normal human kidney and in E a glomerulus of a 25 years old normal human kidney from two patients who underwent nephrectomy for localized renal tumor (Hematoxylin and eosin stain, magnification 40 x. Bars= 20 μm in B and C, bars= 50 μm in D and E).