Growth and division are the two most important processes in plant organogenesis. Cell size results from the dynamic combination of these two processes. Hence studying cell size patterning is crucial to understand organogenesis. The Arabidopsis sepal epidermis is an ideal system to study cell size as it forms a characteristic cell size pattern ranging from cells with only one hundredth the length of the sepal (small cells) to cells with one-fifth the length of the sepal (giant cells). Small cells are produced by ordinary mitosis whereas giant cells are produced by endoreduplication. In my dissertation, I addressed how cell size patterning is generated by genetic and genomic approaches. In my first study, I discovered that the endomembrane trafficking protein SEC24A suppresses endoreduplication in an ACR4, DEK1 and LGO dependent manner. SEC24A, the first identified giant cell formation inhibitor, unraveled a hidden layer of the complicated regulatory network of cell size patterning. In my second study, I applied translating ribosome affinity purification coupled with deep sequencing (TRAP-seq) to systematically discover changes in gene expression between differently sized cells. It was discovered that the giant and small cells have very distinct translatomes, implying they are different cell types. In addition, by comparing the giant cell and another highly endoreduplicated cell type, the trichome, we discovered that although endoreduplication triggers common downstream responses, the giant cell and trichome do have distinct genomic regulation modules. Cell biology and genetics were applied and validated the high-throughput sequencing results.