title: Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.
abstract: Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential.
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research/University Medical Centre Utrecht, Utrecht, The Netherlands. nicholas.barker@imb.a-star.edu.sg
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.forename: Maarten B
authors.initials: MB
authors.lastname: Rookmaaker
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Annie
authors.initials: A
authors.lastname: Ng
authors.forename: Marc
authors.initials: M
authors.lastname: Leushacke
authors.forename: Hugo
authors.initials: H
authors.lastname: Snippert
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Shawna
authors.initials: S
authors.lastname: Tan
authors.forename: Johan H
authors.initials: JH
authors.lastname: Van Es
authors.forename: Meritxell
authors.initials: M
authors.lastname: Huch
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007672:Kidney Cortex / Q000166:cytology / Q000196:embryology; D008138:Loop of Henle / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: C116884:LGR5 protein, human; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled