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First published online February 21, 2008
Stem Cells Vol. 26 No. 5 May 2008, pp. 1265 -1274
doi:10.1634/stemcells.2007-1067; www.StemCells.com
© 2008 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

Hes1 Regulates Corneal Development and the Function of Corneal Epithelial Stem/Progenitor Cells

Takahiro Nakamuraa,b,c, Toshiyuki Ohtsukad, Eiichi Sekiyamaa, Leanne J. Coopere, Hiroshi Kokubud, Nigel J. Fullwoode, Yann Barrandonc, Ryoichiro Kageyamad, Shigeru Kinoshitaa

aDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medicine, Kyoto, Japan;
bResearch Center for Regenerative Medicine, Doshisha University, Kyoto, Japan;
cLaboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
dInstitute for Virus Research, Kyoto University, Kyoto, Japan;
eBiomedical Sciences, Lancaster University, Lancaster, United Kingdom

Key Words. Cornea • Development • Hes • Notch • Stem cell

Correspondence: Takahiro Nakamura M.D., Ph.D., Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-0841 Japan. Telephone: 81-75-251-5578; Fax: 81-75-251-5663; e-mail: tnakamur{at}ophth.kpu-m.ac.jp

Received December 14, 2007; accepted for publication February 12, 2008.
First published online in STEM CELLS EXPRESS   February 21, 2008.



Hes1, a major target gene in Notch signaling, regulates the fate and differentiation of various cell types in many developmental systems. To gain a novel insight into the role of Hes1 in corneal tissue, we performed gain-of-function and loss-of-function studies. We show that corneal development was severely disturbed in Hes1-null mice. Hes1-null corneas manifested abnormal junctional specialization, cell differentiation, and less cell proliferation ability. Worthy of note, Hes1 is expressed mainly in the corneal epithelial stem/progenitor cells and is not detected in the differentiated corneal epithelial cells. Expression of Hes1 is closely linked with corneal epithelial stem/progenitor cell proliferation activity in vivo. Moreover, forced Hes1 expression inhibits the differentiation of corneal epithelial stem/progenitor cells and maintains these cells' undifferentiated state. Our data provide the first evidence that Hes1 regulates corneal development and the homeostatic function of corneal epithelial stem/progenitor cells.

Disclosure of potential conflicts of interest is found at the end of this article.






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