Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development

TY - JOUR

T1 - Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development

AU - Barker, N.

AU - Rookmaaker, M.B.

AU - Kujala, P.

AU - Ng, A.

AU - Leushacke, M.

AU - Snippert, H.

AU - van de Wetering, M.

AU - Tan, S.

AU - van Es, J.H.

AU - Huch, M.

AU - Poulsom, R.

AU - Verhaar, M.C.

AU - Peters, P.J.

AU - Clevers, H.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2012.08.018

DO - 10.1016/j.celrep.2012.08.018

M3 - Article

SN - 2211-1247

VL - 2

SP - 540

EP - 552

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -