CAREER: A Cellular and Molecular Analysis of a Specific Retinal Lineage that Generates Cone Photoreceptors and Horizontal Cells

胚胎从单个细胞发育而来，这个细胞产生具有越来越特殊功能的新细胞。对于每个组织，都有祖细胞，然后祖细胞会产生更多的新细胞来组成该组织。让我们看到颜色的细胞，视锥感光细胞，是由发育中的眼睛中的祖细胞形成的。该项目将重点研究祖细胞如何形成这些光感受器。指导这一过程的信息在DNA中找到。实验将使用参与锥体光感受器形成的特定DNA序列来实时跟踪祖细胞变成成为锥体光感受器的新细胞的过程。这项研究有望为眼睛发育过程中独特细胞的形成带来新的见解。此外，该项目将邀请处于早期阶段的本科生参与这一研究项目，并担任纽约公立学校系统外展活动的负责人。中学生将被介绍给什么是科学家，这将为他们也能成为科学家打开大门。这一职业奖项将允许首席研究员在哈勒姆的一家大型少数族裔服务机构发展可持续的综合研究和推广计划。最近人们认识到，存在视网膜祖细胞群体，它们将产生的细胞类型受到限制。这项研究的目的是调查这些群体中优先产生锥形感光细胞和水平细胞的群体之一。为了实现这一点，将应用多种使用细胞类型特定转录调控元件的方法。在细胞水平上，这些元素将被用来确定由这些祖细胞形成的锥形和水平细胞的亚型。此外，将使用实时成像来分析单个锥体/水平细胞前体细胞的子代命运，以确定谱系的异质性。在分子水平上，Notch-Delta信号通路在这一祖细胞谱系中的作用将被研究。最后，将确定细胞通过锥体/水平细胞祖细胞谱系过渡时的完整转录组和表观基因组特征。在其结论中，该项目有望提供一种新的分子检查的基因定义的视网膜谱系。

An embryo develops from a single cell and this cell generates new cells with increasingly specific functions. For each tissue, there are progenitor cells that then generate more new cells that make up that tissue. Cells that allow us to see color, cone photoreceptors, are formed from progenitor cells in the developing eye. This project will focus on how the progenitor cells form these photoreceptors. The information that directs this process is found in DNA. Experiments will use specific DNA sequences that are involved in the formation of cone photoreceptors to track the progenitor cells in real time as they change into new cells that become cone photoreceptors. This research is expected to lead to new insights into how unique cells are formed during eye development. In addition, this project will engage early stage undergraduates to participate in both this research project and to be leaders of an outreach activity to the New York Public School system. Middle school students will be introduced to what it is to be a scientist, which will open the door to the possibility that they can also become one. This CAREER award will allow the Principal Investigator to develop a sustainable integrated research and outreach program at a large minority serving institution in Harlem.It has recently been recognized that there are retinal progenitor cell populations that are restricted in the cell types that they will generate. The goal of this study is to investigate one of these populations that preferentially generates cone photoreceptors and horizontal cells. To accomplish this, multiple approaches that use cell-type specific transcriptional regulatory elements will be applied. At the cellular level, these elements will be used to determine the subtypes of cone and horizontal cells formed from these progenitor cells. In addition, live imaging will be used to analyze the daughter fates of single cone/horizontal cell progenitors to define the heterogeneity of the lineage. At the molecular level, the role of the Notch-Delta signaling pathway in this progenitor lineage will be examined. Finally, whole transcriptome and epigenome signatures of cells as they transition through the cone/horizontal cell progenitor lineage will be determined. At its conclusion, this project is expected to provide a novel molecular examination of a genetically defined retinal lineage.