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Metabolic Regulation by Core Pluripotency Factors for Maintaining Embryonic Stem Cell Pluripotency : 배아줄기세포의 전분화성 유지를 위한 Core Pluripotency Factor의 대사조절
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 윤홍덕 | - |
dc.contributor.author | 김현수 | - |
dc.date.accessioned | 2017-07-14T01:46:10Z | - |
dc.date.available | 2017-07-14T01:46:10Z | - |
dc.date.issued | 2016-08 | - |
dc.identifier.other | 000000136461 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122326 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2016. 8. 윤홍덕. | - |
dc.description.abstract | Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of LIF. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination.
* This work is published in Stem Cells | - |
dc.description.abstract | published online September, 2015 DOI: 10.1002/stem.2073
---------------------------------------------------------------------------------------------- Keywords: embryonic stem cells, core pluripotency factors, Oct4, metabolism, glycolysis, hexokinase 2 (Hk2), pyruvate kinase M2 (Pkm2), pluripotency, differentiation Student number: 2009-30601 | - |
dc.description.tableofcontents | I. Introduction 1
II. Material and Methods 9 1. Cell culture 10 2. Transplantation assay 10 3. Generation of stable expression of hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2) in ESCs 10 4. Self-renewal assay 11 5. In vitro differentiation of ESCs 12 6. Reporter gene assay 12 7. Western blot and immunofluorescence 12 8. Real-Time qPCR and chromatin immunoprecipitation (ChIP) assay 13 9. Lactate assay 15 10. Extracellular flux analysis 15 11. Flow cytometry (FACS) analysis of SSEA1-positive cells 15 12. Karyotype analysis 16 13. ChIP-sequencing 16 14. RNA-sequencing 17 15. RNA-sequencing data analysis 17 16. Accession numbers 17 17. Statistics 18 III. Results 21 1. Core pluripotency factors regulate a subset of glycolytic enzymes 22 2. Oct4 directly regulates Hk2 and Pkm2 in embryonic stem cells 34 3. Sustaining high levels of glycolysis delays ESC differentiation 39 4. Sustaining high glycolysis levels enables some population of ESCs to retain self-renewal and differentiation potential in the absence of LIF 53 5. Molecular signature of an ESC derivative sustaining high glycolysis levels in the absence of LIF 59 IV. Discussion 68 V. References 74 Abstract in Korean 88 | - |
dc.format | application/pdf | - |
dc.format.extent | 4046459 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | 줄기세포 | - |
dc.subject.ddc | 610 | - |
dc.title | Metabolic Regulation by Core Pluripotency Factors for Maintaining Embryonic Stem Cell Pluripotency | - |
dc.title.alternative | 배아줄기세포의 전분화성 유지를 위한 Core Pluripotency Factor의 대사조절 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Hyunsoo Kim | - |
dc.description.degree | Doctor | - |
dc.citation.pages | 91 | - |
dc.contributor.affiliation | 의과대학 의과학과 | - |
dc.date.awarded | 2016-08 | - |
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