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  Department of Brain Sciences Theses Ph.D.

FASN-dependent lipogenesis links mitochondrial remodeling in human NSCs and neurogenic dynamics in Cerebral Organoids

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dc.contributor.advisor 이성배 -
dc.contributor.author Seulgi Noh -
dc.date.accessioned 2026-01-23T10:53:50Z -
dc.date.available 2026-01-23T10:53:50Z -
dc.date.issued 2026 -
dc.identifier.uri https://scholar.dgist.ac.kr/handle/20.500.11750/59592 -
dc.identifier.uri http://dgist.dcollection.net/common/orgView/200000943424 -
dc.description FASN, Mitochondria, hiPSC, Cerebral organoid, Neuroscience -
dc.description.tableofcontents Ⅰ. INTRODUCTION 1
1.1 Human Brain Development and Neural Stem Cells (NSCs) 1
1.1.1 Overview: Importance of Human Brain Development 1
1.1.2 Roles of NSCs in Brain Development 3
1.2 Lipid Metabolism in NSCs 6
1.2.1 Overview: Lipid Metabolism in NSCs 6
1.2.2 De novo lipogenesis (DNL) via Fatty Acid Synthase (FASN) 7
1.2.3 Lipid Storage and Lipid Droplets (LDs) 9
1.2.4 Fatty-Acid Oxidation (FAO) and Mitochondrial Handling of Lipids 10
1.3 Role of Mitochondria in NSCs 11
1.3.1 State-dependent Remodeling and Signaling 12
1.3.2 Mitochondrial Quality Control and Apoptosis Gating 12
1.3.3 Developmental Context 13
1.3.4 Coupling to Lipid Metabolism 13
1.4 Aim of the Study 14
1.4.1 FASN-Mitochondria Coupling in NSCs and Human Disease: Background and Hypothesis 14
1.4.2 FASN-Dependent Metabolic and Developmental Programs: Experimental Model and Study Design 15
1.4.3 Main questions of this study 15

Ⅱ. MATERIALS AND METHODS 17
2.1 Human-Induced Pluripotent Stem Cells (hiPSCs) culture 17
2.2 Induction of Neural Stem Cells (NSCs) from hiPSCs 17
2.3 FASN knockdown in NSCs 17
2.4 Proliferation rate using IncuCyte 18
2.5 Cellular Lipid Extraction 18
2.6 Lipidomics Analysis by LC–QTOF Mass Spectrometry 19
2.7 Immunocytochemistry (ICC) staining 19
2.8 Live Cell Imaging – TMRM, BODIPY 493/503, MitoSOX 20
2.9 RNA isolation, quantitative RT-PCR (qRT-PCR) 20
2.10 Western blotting 21
2.11 Transmission Electron Microscopy (TEM) in NSCs 21
2.12 TEM and Large-area Scanning Electron Microscopy (SEM) in Cerebral Organoids 22
2.13 Mitochondrial and Glycolytic Function Analysis Using Seahorse XFe24 Extracellular Flux Analyzer 22
2.14 RNA isolation and mRNA Sequencing 24
2.15 Identification of Differentially Expressed Genes (DEGs) 24
2.16 Generation of Cerebral Organoids using hiPSCs 24
2.17 Cerebral Organoids for Cryosection 25
2.18 Immunohistochemistry (IHC) analysis 25
2.19 Imaging Analysis 26
2.20 Statistical Analysis 26

Ⅲ. RESULTS 28
3.1 FASN Is Essential for Maintaining NSC Proliferation and Lipid Homeostasis 28
3.2 FASN Loss Impairs β-Oxidation and Mitochondrial Function in NSCs 29
3.3 FASN Knockdown Alters Mitochondrial Dynamics and Morphology in NSCs 30
3.4 FASN Knockdown Alters Glycolytic Parameters and Promotes Glycogen Accumulation in NSCs 31
3.5 Loss of FASN Leads to Changes in NSC Transcriptional Profiles 33
3.6 FASN Inhibition in Cerebral Organoids Alters Progenitor Proliferation and Cortical Layering 36

Ⅳ. DISCUSSION 39
4.1 Significance of FASN During Neurodevelopment in hiPSC-derived NSC and Cerebral Organoids 39
4.2 Mitochondrial Functional and Structural Alterations Induced by FASN Inhibition in NSCs 40
4.3 Metabolic Reprogramming Associated with FASN Inhibition in NSCs 42
4.4 Reorganization of the Metabolism–Mitochondria–Transcriptome Axis under FASN Deficiency 44
4.5 Integrated Metabolic Regulation and Neural Differentiation in Cerebral Organoids 47
4.6 Significance, Limitations, and Future Directions 48

Ⅴ. REFERENCE 82		 -
dc.format.extent 93 -
dc.language eng -
dc.publisher DGIST -
dc.title FASN-dependent lipogenesis links mitochondrial remodeling in human NSCs and neurogenic dynamics in Cerebral Organoids -
dc.title.alternative FASN 의존적 지방합성에 의해 조절되는 인간 신경줄기세포의 미토콘드리아 재편성과 대뇌 오가노이드 신경발생 역학의 연관성 -
dc.type Thesis -
dc.identifier.doi 10.22677/THESIS.200000943424 -
dc.description.degree Doctor -
dc.contributor.department Department of Brain Sciences -
dc.contributor.coadvisor Ji Young Mun -
dc.date.awarded 2026-02-01 -
dc.publisher.location Daegu -
dc.description.database dCollection -
dc.citation XT.BD 노57 202602 -
dc.date.accepted 2026-01-19 -
dc.contributor.alternativeDepartment 뇌과학과 -
dc.subject.keyword FASN, Mitochondria, hiPSC, Cerebral organoid, Neuroscience -
dc.contributor.affiliatedAuthor Seulgi Noh -
dc.contributor.affiliatedAuthor Sung Bae Lee -
dc.contributor.affiliatedAuthor Ji Young Mun -
dc.contributor.alternativeName 노슬기 -
dc.contributor.alternativeName Sung Bae Lee -
dc.contributor.alternativeName 문지영 -
dc.rights.embargoReleaseDate 2031-02-28 -
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