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Macula densa progenitor cells contribute to nephron formation during kidney development (692.6)
Author(s) -
Burford James,
RiquierBrison Anne,
Villanueva Karie,
PetiPeterdi Janos
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.692.6
Subject(s) - progenitor cell , nephron , biology , renal stem cell , population , stem cell , microbiology and biotechnology , progenitor , kidney , endocrinology , medicine , environmental health
Cells of the macula densa (MD) in the adult kidney are strategically localized in the distal tubule at the glomerular vascular entrance, which mirrors the position of nephron‐committed progenitor cells in the developing kidney, at the interface between the ureteric bud and the metanephric mesenchyme. Indirect evidence suggests that MD cells contribute to nephrogenesis. Here we aimed to assess the stem/progenitor identity of MD cells via in vivo lineage tracing. We developed MD‐Confetti mice with tamoxifen‐inducible expression of the confetti fluorescent reporter construct (CFP/GFP/YFP/RFP) specifically in MD cells by crossing nNOS‐CreERT2 and Confetti/fl mice. Confetti expression was induced by ip tamoxifen injections on postnatal days 2 and 3, and kidneys were harvested three weeks later. MD cells were identified by one of the four Confetti colors, expressing either membrane‐targeted CFP, nuclear‐GFP, cytosolic YFP or RFP. MD plaques usually contained individual MD cells of all four colors. However, in vivo multi‐color lineage tracing identified MD cells as a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb (TAL) of Henle’s loop. In addition to multicolor cell labeling in MD plaques, fluorescence image analysis revealed the presence of several, exclusively clonal (i.e. single‐color) multi‐cell tracing units in TALs. Our results highlight the new role and important contribution of individual MD stem/progenitor cells to nephron formation during kidney development.