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Sowmya Parameswaran, Iqbal Ahmad; HMGA2 regulates the self-renewal of retinal progenitors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2214. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal progenitors unlike neural stem cells do not self-renew under normal culture conditions in vitro. Our recent study demonstrates that retinal progenitors can self-renew, but this property is non-cell autonomous, requiring interactions with other cell types. Here, we have examined the role of non-histone chromosomal high-mobility group protein A2; HMGA2 in the self-renewal.
HMGA2 expression was determined by Q-PCR, immunohistochemistry and Western analysis in embryonic day 18 (E18) progenitors. Its involvement in self-renewal of E18 progenitors was determined by neurosphere assay in the presence of conditioned medium obtained from cultured endothelial cells (ECCM) and Hmga2 siRNA.
To determine the physiological relevance of HMGA2 in retina, we analyzed its temporal expression by Q-PCR, which revealed a temporal decrease in Hmga2 expression during retinal development in vivo. Analysis of spatial localization of HMGA2 by immunohistochemistry on E18 retinal sections showed a center to peripheral gradient of HMGA2 distribution, co-localized with BrdU positive progenitors. Involvement of HMGA2 in self-renewal of retinal progenitors was examined in ECCM generated neurospheres. A significant increase in Hmga2 transcript levels and Hmga2+ BrdU+ cells was observed in ECCM generated neurospheres compared to EGF controls. To determine whether Hmga2 regulatory axis is involved in ECCM mediated self - renewal, HMGA2 expression was attenuated using siRNA lentivirus in E18 retinal dissociates. HMGA2 knockdown led to decrease in the number of neurospheres and BrdU positive cells suggesting the loss of self-renewal. Data on HMGA2 axis involved in self-renewal of retinal progenitors will be provided.
Retinal progenitors display a non-cell autonomous self-renewal property, which is likely to be regulated by a molecular axis, underpinned by HMGA2.
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