title: Frizzled 7 maintains the undifferentiated state of human limbal stem/progenitor cells.
abstract: Wnt signaling pathway plays an important role in the regulation of human limbal stem/progenitor cells (LSCs). To examine the possible function of Frizzled (Fz) receptors in LSCs, the expression of 10 Fz receptors was profiled in the limbus and cornea. Only Fz7 had preferential expression in the basal limbal epithelium which contains the LSCs. The expression of Fz7 was colocalized with the putative LSC markers including p63α, N-cadherin and keratin (K) 14, and was minimum in cells expressing the corneal maturation marker K12. The expression of Fz7 was higher in the enriched LSCs population and decreased in cultured LSCs when there was a loss of progenitor phenotype. When the Fz7 was knocked down (Fz(KD)) using shRNA in primary LSCs, the expression of putative LSC markers ABCG2, ΔNp63α, and K14 was decreased significantly. The colony forming efficiency of the Fz7(KD) LSCs was significantly decreased in the subsequent passage 1 and 2 compared to the control. Our finding suggests that Wnt signaling is one of the factors of LSC niche, and Fz7 helps to maintain the undifferentiated state of LSCs.
authors.affiliation: Jules Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Mei
authors.forename: Martin N
authors.initials: MN
authors.lastname: Nakatsu
authors.forename: Elfren R
authors.initials: ER
authors.lastname: Baclagon
authors.forename: Sophie X
authors.initials: SX
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D016850:Limbus Corneae / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D015820:Cadherins; C115810:FZD7 protein, human; D051157:Frizzled Receptors; C507540:KRT14 protein, human; D053547:Keratin-14; D008565:Membrane Proteins; C111200:SECTM1 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Frizzled; Limbal stem cell deficiency; Limbal stem cells; Niche factor; Wnt signaling pathway