Athera Yakoo
Pronouns: She/Her/Hers
UROP Fellowship: Biomedical and Life Sciences
Research Mentor(s): Lev Prasov, MD, PhD
Research Mentor Institution/Department: Michigan Medicine, Department of Ophthalmology and Visual Sciences
Presentation Date: Wednesday, August 4th
Session: Session 1 (3pm-3:50pm EDT)
Breakout Room: Room 2
Presenter: 2
Abstract
Myrf is a transcription factor that is essential for proper development of the retinal pigmented epithelium (RPE) and the underlying retina. We have previously analyzed mice with a conditional deletion of Myrf in the RPE and identified resulting downstream genetic changes leading to loss of RPE and impaired vision (Garnai et al., 2019). We also identified secondary defects in the retina, loss of rod and cone photoreceptors. As the etiology of these defects is unclear, we used single cell sequencing (scRNAseq) to identify the gene expression changes associated with loss of MYRF in the RPE (Rxcre;Myrffl/fl) at various stages during embryonic and postnatal development. We hypothesize that deletion of Myrf in the RPE leads to secondary transcriptional changes in the retina that impact vision. We have identified 10 clusters of cells as Retinal Progenitor Cells (RPC) and used the Seurat analysis program to identify the unique transcripts within each cluster and assign a cell identity. Within each cell identity and cluster, we generated a list of differentially expressed genes (DEGs) between mutants and controls. Then, we prioritized these lists based on literature searches and identified Dkk3, Neurod1, Fabp7, Otx2, Fgf3, Fgf15, and Prss56 as the most interesting DEGs to characterize. We sectioned Rxcre;Myrffl/fl mutant and control eye tissue from postnatal day 0 (P0) and P3 to confirm the differential expression of our candidate genes by immunohistochemistry or RNAscope in situ hybridization, with initial focus on Dkk3, a retinal progenitor gene involved in eye growth, and Prss56, a gene previously implicated in eye size disorders. We are additionally evaluating cell population changes, and specifically investigating cell death within the RPE. Our work will help to uncover the role of MYRF in RPE development and eye size disorders, which can hopefully be used in the future to develop better treatments for these vision threatening conditions and a better understanding of the mechanism of eye growth.
Authors: Athera Yakoo, Michelle Brinkmeier, Su Qing Wang, Lev Prasov
Research Method: Laboratory Research
https://prasov.lab.medicine.umich.edu/research
