Lgr5 marks cycling, yet long-lived, hair follicle stem cells

被引:746
作者
Jaks, Viljar [1 ,2 ,3 ]
Barker, Nick [4 ]
Kasper, Maria [1 ]
Van Es, Johan H. [4 ]
Snippert, Hugo J. [4 ]
Clevers, Hans [4 ]
Toftgard, Rune [1 ]
机构
[1] Novum, Karolinska Inst, Dept Biosci & Nutr, SE-14157 Huddinge, Sweden
[2] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia
[3] Estonian Bioctr, EE-51010 Tartu, Estonia
[4] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
基金
瑞典研究理事会; 美国国家卫生研究院;
关键词
D O I
10.1038/ng.239
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair follicles. Here we show that Lgr5(+) cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5(+) progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5(+) cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen. Expression analysis suggests involvement of autocrine Hedgehog signaling in maintaining the Lgr5(+) stem cell population.
引用
收藏
页码:1291 / 1299
页数:9
相关论文
共 35 条
  • [1] Murine epidermal label-retaining cells isolated by flow cytometry do not express the stem cell markers CD34, Sca-1, or Flk-1
    Albert, MR
    Foster, RA
    Vogel, JC
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2001, 117 (04) : 943 - 948
  • [2] The hair cycle
    Alonso, L
    Fuchs, E
    [J]. JOURNAL OF CELL SCIENCE, 2006, 119 (03) : 391 - 393
  • [3] Identification of stem cells in small intestine and colon by marker gene Lgr5
    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
    [J]. NATURE, 2007, 449 (7165) : 1003 - U1
  • [4] Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche
    Blanpain, C
    Lowry, WE
    Geoghegan, A
    Polak, L
    Fuchs, E
    [J]. CELL, 2004, 118 (05) : 635 - 648
  • [5] Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis
    Braun, KM
    Niemann, C
    Jensen, UB
    Sundberg, JP
    Silva-Vargas, V
    Watt, FM
    [J]. DEVELOPMENT, 2003, 130 (21): : 5241 - 5255
  • [6] CHASE HB, 1951, PHYSIOL ZOOL, V24, P1
  • [7] Essential role for Sonic hedgehog during hair follicle morphogenesis
    Chiang, C
    Swan, RZ
    Grachtchouk, M
    Bolinger, M
    Ying, LTT
    Robertson, EK
    Cooper, MK
    Gaffield, W
    Westphal, H
    Beachy, PA
    Dlugosz, AA
    [J]. DEVELOPMENTAL BIOLOGY, 1999, 205 (01) : 1 - 9
  • [8] LABEL-RETAINING CELLS RESIDE IN THE BULGE AREA OF PILOSEBACEOUS UNIT - IMPLICATIONS FOR FOLLICULAR STEM-CELLS, HAIR CYCLE, AND SKIN CARCINOGENESIS
    COTSARELIS, G
    SUN, TT
    LAVKER, RM
    [J]. CELL, 1990, 61 (07) : 1329 - 1337
  • [9] Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells
    Depreter, Marianne G. L.
    Blair, Natalie F.
    Gaskell, Terri L.
    Nowell, Craig S.
    Davernt, Kathleen
    Pagliocca, Adelina
    Stenhouse, Frances H.
    Farley, Alison M.
    Fraser, Adrian
    Vrana, Jan
    Robertson, Kevin
    Morahan, Grant
    Tomlinson, Simon R.
    Blackburn, C. Clare
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (03) : 961 - 966
  • [10] DRY FW, 1925, J GENET, V16, P278