Immunohistochemical markers for corneal stem cells in the early developing human eye.
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 mesodermal limbal niche most likely originates. PAX6 was expressed in both ectodermally and mesodermally derived parts of the limbal niche, underscoring the importance of PAX6 in niche formation.
Department of Ophthalmology, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark. mikkel.lyngholm@ki.au.dk
Mikkel
M
Lyngholm
Poul E
PE
Høyer
Henrik
H
Vorum
Kim
K
Nielsen
Niels
N
Ehlers
Kjeld
K
Møllgård
D051398:Aquaporin 1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019573:Epithelium, Corneal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D047109:Fetal Development / Q000502:physiology; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053569:Keratin-15 / Q000378:metabolism; D016850:Limbus Corneae / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D051398:Aquaporin 1; D015415:Biomarkers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D053569:Keratin-15; D009419:Nerve Tissue Proteins; D064231:Nestin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C577484:NES protein, human; C000605730:PAX6 protein, human