Title

Characterization of lung epithelial cell plasticity and its implications for lung diseases by single-cell RNA sequencing

DGIST Authors

Jusung Lee ; June M. Kwak ; Jong Kyoung Kim

Advisor

곽준명

Co-Advisor(s)

Jong Kyoung Kim

Issued Date

2024

Awarded Date

2024-02-01

Citation

Jusung Lee. (2024). Characterization of lung epithelial cell plasticity and its implications for lung diseases by single-cell RNA sequencing. doi: 10.22677/THESIS.200000726941

Type

Thesis

Description

Epithelial plasticity;scRNA-seq;COVID-19;Lung adenocarcinoma;Disease severity

Table Of Contents

Abstract i
List of contents ii
List of figures iv

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

URI

http://hdl.handle.net/20.500.11750/48006
http://dgist.dcollection.net/common/orgView/200000726941

DOI

10.22677/THESIS.200000726941

Degree

Doctor

Department

Department of New Biology

Publisher

DGIST

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