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Andrea Sophia Viczian, Kimberly A Wong, Michael Trembley; Biasing early primitive ectoderm-like cells toward retinal cone photoreceptors. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3578.
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© ARVO (1962-2015); The Authors (2016-present)
In the developing embryo, primitive ectoderm formation is lineage-restricted in response to extrinsic factors. The extrinsic factor, Noggin, plays a key role in inducing retinal cell markers in cultured human embryonic stem (ES) cells. In contrast, mouse ES cells do not express retinal markers when exposed to Noggin. Human ES cells have been shown to share more characteristics with mouse primitive ectoderm than with mouse ES cells. We conducted our study to determine if driving mouse ES cells to a primitive ectoderm lineage would allow them to respond to Noggin, and induce retinal cell markers.
Mouse ES cells were treated with conditioned media and transformed into primitive ectoderm-like (EPL) cells. EPL-induced cells were then treated with Noggin and subsequently grown in differentiation media. Immunocytochemical and qPCR were used to characterize the cells.
If first converted to primitive ectoderm, Noggin treatment resulted in a dose-dependent reduction of pluripotent markers and an increase in neural and retinal progenitor markers. Interestingly, we also found a substantial number of cells expressing markers for cone photoreceptors in the EPL-driven cultures. These results suggest that first restricting mouse ES cells to a primitive ectoderm lineage creates an environment where Noggin can induce retinal cell marker expression.
We are currently determining the underlying molecular mechanism that drives ES cells to retinal progenitors and further, cone photoreceptors
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