Ⅰ. Introduction 1 1.1 Definition of cell plasticity 1 1.2 Cell plasticity across diverse organs 1 1.3 Cell plasticity in tissue damage or disease conditions 3 IⅠ. Unraveling epithelial plasticity in response to SARS-CoV-2 Infection: Insights into variations induced by viral variants and the underlying regulatory mechanisms through scRNA-seq analysis 8 2.1 Disease introduction 8 2.2 Results 11 2.2.1 scRNA-seq profiling unveils the transcriptomic landscape of SARS-CoV-2 infection in the mouse lung 11 2.2.2 Comparing virus infection patterns in the lung over time: Two SARS-CoV-2 strains at single-cell resolution 12 2.2.3 Immune responses of the myeloid compartment to SARS-CoV-2 in the mouse lung 13 2.2.4 Immune responses of the lymphoid compartment to SARS-CoV-2 in the mouse lung 15 2.2.5 Epithelial cell plasticity in the context of SARS-CoV-2 infection 18 2.2.6 Recovery of AT2 transdifferentiation from club cells in the Omicron BA.1 variant infection model 19 2.2.7 Exploring cell-cell interactions to identify factors modulating lung epithelial cell plasticity in SARS-CoV-2 infection response 21 2.3 Methods 22 2.4 Discussion 24 IIⅠ. scRNA-seq reveals cancer cell plasticity and differential regulation in the tumor microenvironment in the Lung Adenocarcinoma across three histologic subtypes 27 3.1 Disease introduction 27 3.2 Results 29 3.2.1 Exploring single-cell transcriptomic landscapes across three distinct histological subtypes of LUAD 29 3.2.2 Characterizing lymphocytes within the TME of LUAD through single-cell transcriptomics across various histologic subtypes 30 3.2.3 Enrichment of exhausted CD8+ T cells in solid-type LUAD compared to other histologic subtypes 31 3.2.4 Enrichment of immunosuppressive and tumor-promoting macrophage subtype (Mac.SPP1.GPNMB) in solid-type LUAD 33 3.2.5 Dysregulation of cholesterol efflux metabolism in the immune system within the TME of solid-type LUAD 34 3.2.6 Elevated Senescence-Associated Secretory Phenotype (SASP) signature in alveolar macrophages of solid-type LUAD 35 3.2.7 Identification of inter-tumoral heterogeneity and diverse cancer cell plasticity across distinct histologic subtypes of LUAD 35 3.2.8 The presence of a minor solid component induces intra-tumoral heterogeneity in A/P patients through clonal evolution 38 3.2.9 Identification of cell-cell interaction patterns specific to histologic subtypes to regulate the cellular plasticity of cancer cells in LUAD 39 3.2.10 Clinical significance 40 3.3 Methods 42 3.4 Discussion 44 IV. References 78 V. 요약문 84