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
来源：
GASTROENTEROLOGY | 2010年 / 138卷 / 05期
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
[71]   Impaired hair placode formation with reduced expression of hair follicle-related genes in mice lacking Lgr4 [J].
Mohri, Yasuaki ;
Kato, Shigeki ;
Umezawa, Akihiro ;
Okuyama, Ryuhei ;
Nishimori, Katsuhiko .
DEVELOPMENTAL DYNAMICS, 2008, 237 (08) :2235-2242
[72]   Prominin1 (CD133) as an Intestinal Stem Cell Marker: Promise and Nuance [J].
Montgomery, Robert K. ;
Shivdasani, Ramesh A. .
GASTROENTEROLOGY, 2009, 136 (07) :2051-2054
[73]   Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC [J].
Morin, PJ ;
Sparks, AB ;
Korinek, V ;
Barker, N ;
Clevers, H ;
Vogelstein, B ;
Kinzler, KW .
SCIENCE, 1997, 275 (5307) :1787-1790
[74]   Neonatal lethality of LGR5 null mice is associated with ankyloglossia and gastrointestinal distension [J].
Morita, H ;
Mazerbourg, S ;
Bouley, DM ;
Luo, CW ;
Kawamura, K ;
Kuwabara, Y ;
Baribault, H ;
Tian, H ;
Hsueh, AJW .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (22) :9736-9743
[75]   Capturing and profiling adult hair follicle stem cells [J].
Morris, RJ ;
Liu, YP ;
Marles, L ;
Yang, ZX ;
Trempus, C ;
Li, SL ;
Lin, JS ;
Sawicki, JA ;
Cotsarelis, G .
NATURE BIOTECHNOLOGY, 2004, 22 (04) :411-417
[76]   Characterization of two fly LGR (leucine-rich repeat-containing, G protein-coupled receptor) proteins homologous to vertebrate glycoprotein hormone receptors: Constitutive activation of wild-type fly LGR1 but not LGR2 in transfected mammalian cells [J].
Nishi, S ;
Hsu, SY ;
Zell, K ;
Hsueh, AJW .
ENDOCRINOLOGY, 2000, 141 (11) :4081-4090
[77]   Lineage and clonal development of gastric glands [J].
Nomura, S ;
Esumi, H ;
Job, C ;
Seong-Seng, T .
DEVELOPMENTAL BIOLOGY, 1998, 204 (01) :124-135
[78]   MOLECULAR-CLONING OF A NOVEL, PUTATIVE-G PROTEIN-COUPLED RECEPTOR FROM SEA-ANEMONES STRUCTURALLY RELATED TO MEMBERS OF THE FSH, TSH, LH/CG RECEPTOR FAMILY FROM MAMMALS [J].
NOTHACKER, HP ;
GRIMMELIKHUIJZEN, CJP .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 197 (03) :1062-1069
[79]   Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche [J].
Ootani, Akifumi ;
Li, Xingnan ;
Sangiorgi, Eugenio ;
Ho, Quoc T. ;
Ueno, Hiroo ;
Toda, Shuji ;
Sugihara, Hajime ;
Fujimoto, Kazuma ;
Weissman, Irving L. ;
Capecchi, Mario R. ;
Kuo, Calvin J. .
NATURE MEDICINE, 2009, 15 (06) :1-U140
[80]   Use of the dissociating enzyme thermolysin to generate viable human normal intestinal epithelial cell cultures [J].
Perreault, N ;
Beaulieu, JF .
EXPERIMENTAL CELL RESEARCH, 1996, 224 (02) :354-364
3456789101112