Brief Report: CD24 and CD44 Mark Human Intestinal Epithelial Cell Populations with Characteristics of Active and Facultative Stem Cells

被引:82
作者
Gracz, Adam D. [1 ,2 ]
Fuller, Megan K. [3 ,6 ]
Wang, Fengchao [5 ]
Li, Linheng [5 ]
Stelzner, Matthias [7 ]
Dunn, James C. Y. [7 ]
Martin, Martin G. [8 ]
Magness, Scott T. [1 ,2 ,4 ]
机构
[1] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Chapel Hill, NC 27599 USA
[5] Stowers Inst Med Res, Kansas City, MO USA
[6] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA
[7] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA
[8] Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol, Los Angeles, CA 90024 USA
基金
美国国家卫生研究院;
关键词
Tissue-specific stem cells; Cell surface markers; Fluorescence-activated cell sorting; Flow cytometry; Cell culture; EXPRESSION MARKS; EXPANSION; ORGANOIDS; COLON;
D O I
10.1002/stem.1391
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Recent seminal studies have rapidly advanced the understanding of intestinal epithelial stem cell (IESC) biology in murine models. However, the lack of techniques suitable for isolation and subsequent downstream analysis of IESCs from human tissue has hindered the application of these findings toward the development of novel diagnostics and therapies with direct clinical relevance. This study demonstrates that the cluster of differentiation genes CD24 and CD44 are differentially expressed across LGR5 positive active stem cells as well as HOPX positive facultative stem cells. Fluorescence-activated cell sorting enables differential enrichment of LGR5 (CD24-/CD44+) and HOPX (CD24+/CD44+) cells for gene expression analysis and culture. These findings provide the fundamental methodology and basic cell surface signature necessary for isolating and studying intestinal stem cell populations in human physiology and disease. STEM Cells2013;31:2024-2030
引用
收藏
页码:2024 / 2030
页数:7
相关论文
共 19 条
[1]
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
[2]
Redundant Sources of Wnt Regulate Intestinal Stem Cells and Promote Formation of Paneth Cells [J].
Farin, Henner F. ;
Van Es, Johan H. ;
Clevers, Hans .
GASTROENTEROLOGY, 2012, 143 (06) :1518-+
[3]
Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro [J].
Gracz, Adam D. ;
Ramalingam, Sendhilnathan ;
Magness, Scott T. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2010, 298 (05) :G590-G600
[4]
Isolation and in vitro expansion of human colonic stem cells [J].
Jung, Peter ;
Sato, Toshiro ;
Merlos-Suarez, Anna ;
Barriga, Francisco M. ;
Iglesias, Mar ;
Rossell, David ;
Auer, Herbert ;
Gallardo, Mercedes ;
Blasco, Maria A. ;
Sancho, Elena ;
Clevers, Hans ;
Batlle, Eduard .
NATURE MEDICINE, 2011, 17 (10) :1225-1227
[5]
Monoclonal Antibodies Against Lgr5 Identify Human Colorectal Cancer Stem Cells [J].
Kemper, Kristel ;
Prasetyanti, Pramudita R. ;
De Lau, Wim ;
Rodermond, Hans ;
Clevers, Hans ;
Medema, Jan Paul .
STEM CELLS, 2012, 30 (11) :2378-2386
[6]
Intestinal Subepithelial Myofibroblasts Support in vitro and in vivo Growth of Human Small Intestinal Epithelium [J].
Lahar, Nicholas ;
Lei, Nan Ye ;
Wang, Jiafang ;
Jabaji, Ziyad ;
Tung, Stephaine C. ;
Joshi, Vaidehi ;
Lewis, Michael ;
Stelzner, Matthias ;
Martin, Martin G. ;
Dunn, James C. Y. .
PLOS ONE, 2011, 6 (11)
[7]
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells [J].
Montgomery, Robert K. ;
Carlone, Diana L. ;
Richmond, Camilla A. ;
Farilla, Loredana ;
Kranendonk, Mariette E. G. ;
Henderson, Daniel E. ;
Baffour-Awuah, Nana Yaa ;
Ambruzs, Dana M. ;
Fogli, Laura K. ;
Algra, Selma ;
Breault, David T. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (01) :179-184
[8]
The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers [J].
Munoz, Javier ;
Stange, Daniel E. ;
Schepers, Arnout G. ;
van de Wetering, Marc ;
Koo, Bon-Kyoung ;
Itzkovitz, Shalev ;
Volckmann, Richard ;
Kung, Kevin S. ;
Koster, Jan ;
Radulescu, Sorina ;
Myant, Kevin ;
Versteeg, Rogier ;
Sansom, Owen J. ;
van Es, Johan H. ;
Barker, Nick ;
van Oudenaarden, Alexander ;
Mohammed, Shabaz ;
Heck, Albert J. R. ;
Clevers, Hans .
EMBO JOURNAL, 2012, 31 (14) :3079-3091
[9]
The Pan-ErbB Negative Regulator Lrig1 Is an Intestinal Stem Cell Marker that Functions as a Tumor Suppressor [J].
Powell, Anne E. ;
Wang, Yang ;
Li, Yina ;
Poulin, Emily J. ;
Means, Anna L. ;
Washington, Mary K. ;
Higginbotham, James N. ;
Juchheim, Alwin ;
Prasad, Nripesh ;
Levy, Shawn E. ;
Guo, Yan ;
Shyr, Yu ;
Aronow, Bruce J. ;
Haigis, Kevin M. ;
Franklin, Jeffrey L. ;
Coffey, Robert J. .
CELL, 2012, 149 (01) :146-158
[10]
Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett's Epithelium [J].
Sato, Toshiro ;
Stange, Daniel E. ;
Ferrante, Marc ;
Vries, Robert G. J. ;
van Es, Johan H. ;
van den Brink, Stieneke ;
van Houdt, Winan J. ;
Pronk, Apollo ;
van Gorp, Joost ;
Siersema, Peter D. ;
Clevers, Hans .
GASTROENTEROLOGY, 2011, 141 (05) :1762-1772