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ABSTRACT: Classifying and characterizing cell types and cell states has emerged as a high priority for biologists to understand the form, function and dysfunction of complex tissues such as the brain. While cell classification has a rich history, recent technological advances have made it possible to tackle this problem systematically and comprehensively, and test the foundations underlying the concept of a “cell taxonomy”. I have addressed these issues in the mammalian retina, a complex yet accessible part of the brain, using hight-hroughput single-cell RNA-seq. I will describe a nearly complete cell taxonomy of the mouse retina (~140 neuronal types), and discuss the extent to which molecularly defined types correspond to types defined by traditional morphological and physiological criteria. I will then describe recent efforts to use the mouse retinal taxonomy as a foundation to, (1) assess cell-intrinsic and non-autonomous features that mediate selective resilience of neuronal types in injury models, (2) generate taxonomies of non-human primates and humans, and (3) explore conservation of cell types across species. I will describe major computational innovations for single-cell transcriptomic analysis developed in these studies that are applicable to similar efforts in other systems.BIO: Shekhar is a postdoctoral fellow at the Broad Institute of Massachusetts Institute of Technology and Harvard University, associated with the group of Professor Aviv Regev. He earned his Ph.D. in chemical engineering at MIT with Professor Arup Chakraborty, working at the interface of physics, computation and immunology. His present work combines genomic measurements and statistical learning techniques to understand the cellular organization of complex tissues. In recent work with experimental collaborators, he applied massively parallel single-cell genomics to generate a complete molecular atlas of neuronal types in the mouse retina. He is presently using it as a foundational tool to explore cell type development, evolution and cell-type specific responses to pathologies. He was recently awarded the National Institutes of HealthPathway to Independence Award (K99).