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Engineering Pluripotent Stem Cell Heterogeneity and Its Effects on Differentiation
Engineering Pluripotent Stem Cell Heterogeneity and Its Effects on Differentiation
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105654
- ISBN
- 9798265452887
- DDC
- 610
- 서명/저자
- Engineering Pluripotent Stem Cell Heterogeneity and Its Effects on Differentiation
- 발행사항
- [Sl] : University of Illinois at Urbana-Champaign, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 98 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Kong, Hyunjoon.
- 학위논문주기
- Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2024.
- 초록/해제
- 요약Pluripotent stem cells (PSCs) have the potential to revolutionize both fundamental and applied bioscience studies, yet their applications have been limited due to their heterogeneity. Stem cell heterogeneity can lead to several challenges, such as differentiation into undesired cell types, compromised functionality, and the growth of cancerous tumors. Therefore, despite nearly a century of stem cell research, the FDA has only approved hematopoietic stem cells for therapeutic applications. It is essential to understand and regulate the mechanism of heterogeneity for enhanced stem cell engineering. To this end, we developed and optimized a reliable and cost-effective method using flow cytometry, allowing us to analyze multiple samples with various treatments at the single-cell level for population heterogeneity. With the established quantification methodology, we implemented a heuristic approach to identify potential mechanisms that may influence heterogeneity. The screened mechanisms spanned a broad range of disciplines, from modulating the growth substrate's stiffness to inhibiting DNA gene expression regulatory mechanisms to controlling cell properties such as cell cycle. We are the first to demonstrate that modulation of the cell cycle could induce a consistent and significant effect on the pluripotent gene expression. PSCs with modulated cell cycles were then differentiated into cardiac and motor neuron lineages. We present a novel finding: partial cell cycle arrest, compared to untreated and near-complete arrest conditions, significantly enhanced the functionality of differentiated tissues. In addition to demonstrating a novel methodology for enhancing stem cell differentiation, these findings suggest that much remains to be understood about how heterogeneity influences differentiation. The work presented lays a foundational methodology for further investigating and engineering pluripotent heterogeneity and investigating its effects on differentiation.
- 일반주제명
- Biomedical engineering
- 일반주제명
- Cellular biology
- 일반주제명
- Molecular biology
- 일반주제명
- Bioengineering
- 일반주제명
- Genetics
- 키워드
- Stem cells
- 키워드
- Cardiac tissue
- 기타저자
- University of Illinois at Urbana-Champaign Bioengineering
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798265452887
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■035 ▼a(MiAaPQ)124561
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aWang, Jason Xiao.
■24510▼aEngineering Pluripotent Stem Cell Heterogeneity and Its Effects on Differentiation
■260 ▼a[Sl]▼bUniversity of Illinois at Urbana-Champaign▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a98 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Kong, Hyunjoon.
■5021 ▼aThesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2024.
■520 ▼aPluripotent stem cells (PSCs) have the potential to revolutionize both fundamental and applied bioscience studies, yet their applications have been limited due to their heterogeneity. Stem cell heterogeneity can lead to several challenges, such as differentiation into undesired cell types, compromised functionality, and the growth of cancerous tumors. Therefore, despite nearly a century of stem cell research, the FDA has only approved hematopoietic stem cells for therapeutic applications. It is essential to understand and regulate the mechanism of heterogeneity for enhanced stem cell engineering. To this end, we developed and optimized a reliable and cost-effective method using flow cytometry, allowing us to analyze multiple samples with various treatments at the single-cell level for population heterogeneity. With the established quantification methodology, we implemented a heuristic approach to identify potential mechanisms that may influence heterogeneity. The screened mechanisms spanned a broad range of disciplines, from modulating the growth substrate's stiffness to inhibiting DNA gene expression regulatory mechanisms to controlling cell properties such as cell cycle. We are the first to demonstrate that modulation of the cell cycle could induce a consistent and significant effect on the pluripotent gene expression. PSCs with modulated cell cycles were then differentiated into cardiac and motor neuron lineages. We present a novel finding: partial cell cycle arrest, compared to untreated and near-complete arrest conditions, significantly enhanced the functionality of differentiated tissues. In addition to demonstrating a novel methodology for enhancing stem cell differentiation, these findings suggest that much remains to be understood about how heterogeneity influences differentiation. The work presented lays a foundational methodology for further investigating and engineering pluripotent heterogeneity and investigating its effects on differentiation.
■590 ▼aSchool code: 0090.
■650 4▼aBiomedical engineering
■650 4▼aCellular biology
■650 4▼aMolecular biology
■650 4▼aBioengineering
■650 4▼aGenetics
■653 ▼aStem cells
■653 ▼aStochastic gene expression
■653 ▼aCardiac tissue
■653 ▼aMotor neuron lineages
■653 ▼aSmall molecule inhibitors
■690 ▼a0541
■690 ▼a0202
■690 ▼a0379
■690 ▼a0369
■690 ▼a0307
■71020▼aUniversity of Illinois at Urbana-Champaign▼bBioengineering.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0090
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17361026▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
