Lgr5+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development

Nick Barker; Maarten B. Rookmaaker; Pekka Kujala; Annie Ng; Marc Leushacke; Hugo Snippert; Marc van de Wetering; Shawna Tan; Johan H. Van Es; Meritxell Huch; Richard Poulsom; Marianne C. Verhaar; Peter J. Peters; Hans Clevers

doi:10.1016/j.celrep.2012.08.018

Lgr5^+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development

Nick Barker^*, Maarten B. Rookmaaker, Pekka Kujala, Annie Ng, Marc Leushacke, Hugo Snippert, Marc van de Wetering, Shawna Tan, Johan H. Van Es, Meritxell Huch, Richard Poulsom, Marianne C. Verhaar, Peter J. Peters, Hans Clevers

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

176 Citations (Scopus)

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

Original language	English
Pages (from-to)	540-552
Number of pages	13
Journal	Cell Reports [E]
Volume	2
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2012.08.018
Publication status	Published - 27 Sept 2012

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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",

author = "Nick Barker and Rookmaaker, {Maarten B.} and Pekka Kujala and Annie Ng and Marc Leushacke and Hugo Snippert and {van de Wetering}, Marc and Shawna Tan and {Van Es}, {Johan H.} and Meritxell Huch and Richard Poulsom and Verhaar, {Marianne C.} and Peters, {Peter J.} and Hans Clevers",

note = "Funding Information: We thank Harry Begthel, Maaike van den Born, and Jeroen Korving for help with the histology, and Nico Ong for help with electron microscopy imaging. H.C. was supported by Koninklijke Nederlandse Akademie Van Wetenschappen program grant PF-HUBR-2007-3956. N.B., A.N., M.L., and S.T. were supported by the Agency for Science, Technology and Research (A ∗ STAR), Singapore. ",

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doi = "10.1016/j.celrep.2012.08.018",

language = "English",

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AU - Barker, Nick

AU - Rookmaaker, Maarten B.

AU - Kujala, Pekka

AU - Ng, Annie

AU - Leushacke, Marc

AU - Snippert, Hugo

AU - van de Wetering, Marc

AU - Tan, Shawna

AU - Van Es, Johan H.

AU - Huch, Meritxell

AU - Poulsom, Richard

AU - Verhaar, Marianne C.

AU - Peters, Peter J.

AU - Clevers, Hans

N1 - Funding Information: We thank Harry Begthel, Maaike van den Born, and Jeroen Korving for help with the histology, and Nico Ong for help with electron microscopy imaging. H.C. was supported by Koninklijke Nederlandse Akademie Van Wetenschappen program grant PF-HUBR-2007-3956. N.B., A.N., M.L., and S.T. were supported by the Agency for Science, Technology and Research (A ∗ STAR), Singapore.

PY - 2012/9/27

Y1 - 2012/9/27

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

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Lgr5^+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development

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