Immunohistochemical markers for corneal stem cells in the early developing human eye

被引:24
作者
Lyngholm, Mikkel [1 ]
Hoyer, Poul E. [2 ]
Vorum, Henrik [1 ]
Nielsen, Kim [1 ]
Ehlers, Niels [1 ]
Mollgard, Kjeld [2 ]
机构
[1] Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus C, Denmark
[2] Univ Copenhagen, Panum Inst, Dev Biol Unit, Dept Cellular & Mol Med, DK-2200 Copenhagen N, Denmark
关键词
corneal stem cells; limbal niche; eye development; human; SOD2; CK15; PAX6;
D O I
10.1016/j.exer.2008.05.004
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The corneal epithelium is continuously being renewed. Differentiated epithelial cells originate from limbal stem cells (LSCs) located in the periphery of the cornea, the corneoscleral limbus. We have recently identified superoxide dismutase 2 (SOD2) and cytokeratin (CK) 15 as limbal basal cell markers and potential markers for LSCs and early transient amplifying cells in human adults. in this Study, we describe the development of the ectodermally derived LSCs and the mesodermally derived niche cells from the time at which the cornea is defined (week 6) until the formation of the early limbal niche (week 14) in human embryos and fetuses. The expression of SOD2 and CK15 was investigated together with other recently identified limbal proteins. Previously suggested LSC and differentiation markers (PAX6, aquaporin-1 and nestin) were also investigated. Both SOD2 and CK15 were present in the corneal epithelium from week 6. However, in week 14 they were predominantly expressed in the limbal epithelium. Both proteins were expressed already from week 7 in a stromal triangular region from which the early meso-dermal limbal niche most likely originates. PAX6 was expressed in both ectodermally and meso-dermally derived parts of the limbal niche, underscoring the importance of PAX6 in niche formation. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:115 / 121
页数:7
相关论文
共 49 条
[1]   Periderm cells form cornified cell envelope in their regression process during human epidermal development [J].
Akiyama, M ;
Smith, LT ;
Yoneda, K ;
Holbrook, KA ;
Hohl, D ;
Shimizu, H .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 112 (06) :903-909
[2]  
BAHN CF, 1984, OPHTHALMOLOGY, V91, P558
[3]   Concise review:: Regulation of embryonic stem cell lineage commitment by mitogen-activated protein kinases [J].
Binetruy, Bernard ;
Heasley, Lynn ;
Bost, Frederic ;
Caron, Leslie ;
Aouadi, Myriam .
STEM CELLS, 2007, 25 (05) :1090-1095
[4]   Cell proliferation during the early stages of human eye development [J].
Bozanic, D ;
Saraga-Babic, M .
ANATOMY AND EMBRYOLOGY, 2004, 208 (05) :381-388
[5]   Role of apoptosis and mitosis during human eye development [J].
Bozanic, D ;
Tafra, R ;
Saraga-Babic, M .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2003, 82 (08) :421-429
[6]   Involvement of cytoskelatal proteins and growth factor receptors during development of the human eye [J].
Bozanic, Darka ;
Bocina, Ivana ;
Saraga-Babic, Mirna .
ANATOMY AND EMBRYOLOGY, 2006, 211 (05) :367-377
[7]   Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells [J].
Budak, MT ;
Alpdogan, OS ;
Zhou, MY ;
Lavker, RM ;
Akinci, MAM ;
Wolosin, JM .
JOURNAL OF CELL SCIENCE, 2005, 118 (08) :1715-1724
[8]   Characterization of putative stem cell phenotype in human limbal epithelia [J].
Chen, Z ;
De Paiva, CS ;
Luo, LH ;
Kretzer, FL ;
Pflugfelder, SC ;
Li, DQ .
STEM CELLS, 2004, 22 (03) :355-366
[9]   The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo [J].
Collinson, JM ;
Quinn, JC ;
Hill, RE ;
West, JD .
DEVELOPMENTAL BIOLOGY, 2003, 255 (02) :303-312
[10]   ABCG2 transporter identifies a population of clonogenic human limbal epithelial cells [J].
De Paiva, CS ;
Chen, Z ;
Corrales, RM ;
Pflugfelder, SC ;
Li, DQ .
STEM CELLS, 2005, 23 (01) :63-73