The identification of effectors of retinal cell fate determination through single cell transcriptomics

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2015-01-01
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Goetz, Jillian
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Jeffrey M. Trimarchi
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Abstract

The vertebrate retina is an exquisite model for neurogenesis, with its common pool of retinal progenitors differentiating into six neuronal cell types and one glial variety, each of which interconnects to form a simply organized yet complexly functioning sensory tissue. Our long-term aim is to determine the cell-autonomous genetic programs that drive retinogenesis, but identifying these signals is complicated by many factors. First, retinal progenitor cells generate the various retinal cell types at distinct but overlapping time points, potentially obscuring the progression of cell-intrinsic signals over time. Second, signals that drive the development of rare, but functionally critical, neuronal subtypes can be drowned out by the genes present in more common and transcriptomically homogeneous cellular populations. For these reasons, we have opted to study the transcriptomes of retinal progenitors at the resolution of the individual cell. Using single-cell transcriptomics, we have isolated genes that are present in subsets of developing retinal progenitors, including the Onecut family of transcription factors and a Polo-like kinase (Plk3), and studied the roles these genes play in the production of specific retinal neurons. We have also expanded our studies to include another vertebrate model system, the chicken, to better identify developmentally relevant genes that have been conserved throughout vertebrate evolution. Through the use of these transcriptomic techniques, my studies detailed in this thesis have brought us closer to elucidating the complex process of retinogenesis.

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Theses & dissertations (Interdisciplinary)
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dissertation
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Thu Jan 01 00:00:00 UTC 2015
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