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A. J. Wong, S. Singhal, C. W. Guo, B. Bhatia, P. T. Khaw, G. A. Limb; Modulation of Hedgehog Signaling Molecules in Adult Human Müller Stem Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1267. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
An important factor expressed by retinal progenitors in the mammalian eye is sonic hedgehog (SHH), a signaling protein that has been shown to regulate processes of embryonic patterning and neural development. A subpopulation of Müller cells have been shown to exhibit stem cell characteristics and these cells can be induced by growth factors to differentiate into retinal neurons in vitro. The purpose of these experiments was to investigate the possible role of the hedgehog (Hh) signaling cascade in modulating adult human Müller stem cell progenicity.
MIO-M1 Müller stem cells, originally derived from cadaveric adult human retina, were cultured in vitro in the presence of fibroblast growth factor 2 (FGF2) and matrigel. Expression of components of the Hh signaling cascade, including GLI2, GLI3, PTCH1, PTCH2, as well as SHH, was examined by RT-PCR, Western blot analysis, and immunohistochemical techniques.
MIO-M1 Müller stem cells constitutively express mRNA transcripts for GLI1, GLI2, GLI3, PTCH1, PTCH2, and SHH. GLI1 and GLI2 were consistently downregulated by culturing the cells for 7 days on matrigel in the presence of FGF2. PTCH1 was not modified by the culture conditions used whereas PTCH2 was slightly decreased by FGF2 and matrigel. Expression of SHH was also decreased by culturing the cells under the same conditions. The downregulation of these factors was related to the proliferative ability of these cells as judged by the expression of the proliferative antigen Ki-67.
From the present observations, it is possible to suggest that growth factors and extracellular matrix proteins that are known to modulate Müller stem cell differentiation are also able to modulate Hh signaling mechanisms. This indicates that the Hh signaling cascade may also regulate processes of differentiation observed in adult human Müller stem cells.
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