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

被引：174

作者：

Barker, Nick ^{[1
,2
]}

Rookmaaker, Maarten B. ^{[3
]}

Kujala, Pekka ^{[4
]}

Ng, Annie ^{[2
]}

Leushacke, Marc ^{[2
]}

Snippert, Hugo ^{[1
]}

van de Wetering, Marc ^{[1
]}

Tan, Shawna ^{[2
]}

Van Es, Johan H. ^{[1
]}

Huch, Meritxell ^{[1
]}

Poulsom, Richard ^{[5
,6
,7
]}

Verhaar, Marianne C. ^{[3
]}

Peters, Peter J. ^{[4
]}

Clevers, Hans ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands

[2] Inst Med Biol, Singapore 138648, Singapore

[3] Univ Med Ctr, NL-3584 CX Utrecht, Netherlands

[4] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands

[5] CRUK London Res Inst, Histopathol Lab, London WC2A 2LY, England

[6] CRUK London Res Inst, ISH Serv, London WC2A 2LY, England

[7] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England

来源：

CELL REPORTS | 2012年 / 2卷 / 03期

关键词：

WNT/BETA-CATENIN; STEM-CELLS; PROGENITOR POPULATION; MAMMALIAN KIDNEY; SMALL-INTESTINE; SELF-RENEWAL; MICE; LGR5; MORPHOGENESIS; REGENERATION;

D O I：

10.1016/j.celrep.2012.08.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：540 / 552

页数：13

共 45 条

[1] Very Long-term Self-renewal of Small Intestine, Colon, and Hair Follicles from Cycling Lgr5+ve Stem Cells [J].

Barker, N. ;

van Es, J. H. ;

Jaks, V. ;

Kasper, M. ;

Snippert, H. ;

Toftgard, R. ;

Clevers, H. .

CONTROL AND REGULATION OF STEM CELLS, 2008, 73 :351-+

[2] Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].

Barker, Nick ;

van Es, Johan H. ;

Kuipers, Jeroen ;

Kujala, Pekka ;

van den Born, Maaike ;

Cozijnsen, Miranda ;

Haegebarth, Andrea ;

Korving, Jeroen ;

Begthel, Harry ;

Peters, Peter J. ;

Clevers, Hans .

NATURE, 2007, 449 (7165) :1003-U1

[3] Tissue-Resident Adult Stem Cell Populations of Rapidly Self-Renewing Organs [J].

Barker, Nick ;

Bartfeld, Sina ;

Clevers, Hans .

CELL STEM CELL, 2010, 7 (06) :656-670

[4] Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro [J].

Barker, Nick ;

Huch, Meritxell ;

Kujala, Pekka ;

van de Wetering, Marc ;

Snippert, Hugo J. ;

van Es, Johan H. ;

Sato, Toshiro ;

Stange, Daniel E. ;

Begthel, Harry ;

van den Born, Maaike ;

Danenberg, Esther ;

van den Brink, Stieneke ;

Korving, Jeroen ;

Abo, Arie ;

Peters, Peter J. ;

Wright, Nick ;

Poulsom, Richard ;

Clevers, Hans .

CELL STEM CELL, 2010, 6 (01) :25-36

[5] Renal Medicine 3 Kidney regeneration [J].

Benigni, Ariela ;

Morigi, Marina ;

Remuzzi, Giuseppe .

LANCET, 2010, 375 (9722) :1310-1317

[6] Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia [J].

Boyle, Scott ;

Misfeldt, Andrew ;

Chandler, Kelly J. ;

Deal, Karen K. ;

Southard-Smith, E. Michelle ;

Mortlock, Douglas P. ;

Baldwin, H. Scott ;

de Caestecker, Mark .

DEVELOPMENTAL BIOLOGY, 2008, 313 (01) :234-245

[7] Canonical WNT/β-catenin signaling is required for ureteric branching [J].

Bridgewater, Darren ;

Cox, Brian ;

Cain, Jason ;

Lau, Agnes ;

Athaide, Valerie ;

Gill, Paul S. ;

Kuure, Satu ;

Sainio, Kirsi ;

Rosenblum, Norman D. .

DEVELOPMENTAL BIOLOGY, 2008, 317 (01) :83-94

[8] R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling [J].

Carmon, Kendra S. ;

Gong, Xing ;

Lin, Qiushi ;

Thomas, Anthony ;

Liu, Qingyun .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (28) :11452-11457

[9] Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system [J].

Carroll, TJ ;

Park, JS ;

Hayashi, S ;

Majumdar, A ;

McMahon, AP .

DEVELOPMENTAL CELL, 2005, 9 (02) :283-292

[10]

Cho EA, 1998, DEVELOPMENT, V125, P803

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