Leucine-Rich Repeat-Containing G-Protein-Coupled Receptors as Markers of Adult Stem Cells

被引:289
作者
Barker, Nick [1 ]
Clevers, Hans
机构
[1] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
关键词
Lgr5; Lgr6; Stem Cell Marker; GPCR; MOUSE SMALL-INTESTINE; HUMAN HEPATOCELLULAR CARCINOMAS; GLYCOPROTEIN HORMONE-RECEPTORS; COLORECTAL-CANCER CELLS; MALE REPRODUCTIVE-TRACT; BETA-CATENIN MUTATIONS; LABEL-RETAINING CELLS; HAIR FOLLICLE BULGE; EPITHELIAL-CELLS; SELF-RENEWAL;
D O I
10.1053/j.gastro.2010.03.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Molecular markers are used to characterize and track adult stem cells. Colon cancer research has led to the identification of 2 related receptors, leucine-rich repeat-containing, G-protein-coupled receptors (Lgr)5 and Lgr6, that are expressed by small populations of cells in a variety of adult organs. Genetic mouse models have allowed the visualization, isolation, and genetic marking of Lgr5(+ve) and Lgr6(+ve) cells and provided evidence that they are stem cells. The Lgr5(+ve) cells were found to occupy locations not commonly associated with stem cells in the stomach, small intestine, colon, and hair follicles. A multipotent population of skin stem cells express Lgr6. Single Lgr5(+ve) stem cells from the small intestine and the stomach can be cultured into long-lived organoids. Further studies of these markers might reveal adult stem cell populations in additional tissues. Identification of the ligands for Lgr5 and 6 will help elucidate stem cell functions and modes of intracellular signaling.
引用
收藏
页码:1681 / 1696
页数:16
相关论文
共 113 条
[61]   DYNAMIC HISTOLOGY OF THE ANTRAL EPITHELIUM IN THE MOUSE STOMACH .4. ULTRASTRUCTURE AND RENEWAL OF GLAND-CELLS [J].
LEE, ER ;
LEBLOND, CP .
AMERICAN JOURNAL OF ANATOMY, 1985, 172 (03) :241-259
[62]   Defining brain wiring patterns and mechanisms through gene trapping in mice [J].
Leighton, PA ;
Mitchell, KJ ;
Goodrich, LV ;
Lu, XW ;
Pinson, K ;
Scherz, P ;
Skarnes, WC ;
Tessler-Lavigne, M .
NATURE, 2001, 410 (6825) :174-179
[63]   G protein-coupled receptor 48 upregulates estrogen receptor α expression via cAMP/PKA signaling in the male reproductive tract [J].
Li, Xiao-Ying ;
Lu, Yan ;
Sun, Hai-Yan ;
Wang, Ji-Qiu ;
Yang, Jun ;
Zhang, Hui-Jie ;
Fan, Neng-Guang ;
Xu, Jia ;
Jiang, Jing-Jing ;
Liu, Ru-Ya ;
Li, Da-Li ;
Liu, Ming-Yao ;
Ning, Guang .
DEVELOPMENT, 2010, 137 (01) :151-157
[64]   Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2 [J].
Luo, CW ;
Dewey, EM ;
Sudo, S ;
Ewer, J ;
Hsu, SY ;
Honegger, HW ;
Hsueh, AJW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (08) :2820-2825
[65]   Regulation of bone formation and remodeling by G-protein-coupled receptor 48 [J].
Luo, Jian ;
Zhou, Wei ;
Zhou, Xin ;
Li, Dali ;
Weng, Jinsheng ;
Yi, Zhengfang ;
Cho, Sung Gook ;
Li, Chenghai ;
Yi, Tingfang ;
Wu, Xiushan ;
Li, Xiao-Ying ;
de Crombrugghe, Benoit ;
Hoeoek, Magnus ;
Liu, Mingyao .
DEVELOPMENT, 2009, 136 (16) :2747-2756
[66]   Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality [J].
Mazerbourg, S ;
Bouley, DM ;
Sudo, S ;
Klein, CA ;
Zhang, JV ;
Kawamura, K ;
Goodrich, LV ;
Rayburn, H ;
Tessier-Lavigne, M ;
Hsueh, AJW .
MOLECULAR ENDOCRINOLOGY, 2004, 18 (09) :2241-2254
[67]   Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors [J].
McClanahan, Terrill ;
Koseoglu, Sandra ;
Smith, Kathleen ;
Grein, Jeffrey ;
Gustafson, Eric ;
Black, Stuart ;
Kirschmeier, Paul ;
Samatar, Ahmed A. .
CANCER BIOLOGY & THERAPY, 2006, 5 (04) :419-426
[68]   Mechanisms of field cancerization in the human stomach: The expansion and spread of mutated gastric stem cells [J].
Mcdonald, Stuart A. C. ;
Greaves, Laura C. ;
Gutierrez-Gonzalez, Lydia ;
Rodriguez-Justo, Manuel ;
Deheragoda, Maesha ;
Leedham, Simon J. ;
Taylor, Robert W. ;
Lee, Chung Yin ;
Preston, Sean L. ;
Lovell, Matthew ;
Hunt, Toby ;
Elia, George ;
Oukrif, Dahmane ;
Harrison, Rebecca ;
Novelli, Marco R. ;
Mitchell, Ian ;
Stoker, David L. ;
Turnbull, Douglass M. ;
Jankowski, Janusz A. Z. ;
Wright, Nicholas A. .
GASTROENTEROLOGY, 2008, 134 (02) :500-510
[69]   Defective postnatal development of the male reproductive tract in LGR4 knockout mice [J].
Mendive, F ;
Laurent, P ;
Van Schoore, G ;
Skarnes, W ;
Pochet, R ;
Vassart, G .
DEVELOPMENTAL BIOLOGY, 2006, 290 (02) :421-434
[70]   Drosophila molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2 [J].
Mendive, FM ;
Van Loy, T ;
Claeysen, S ;
Poels, J ;
Williamson, M ;
Hauser, F ;
Grimmelikhuijzen, CJP ;
Vassart, G ;
Broeck, JV .
FEBS LETTERS, 2005, 579 (10) :2171-2176