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Stem Cell Models of Axial Patterning and Their Implications for V2a Neurons and Engineered Neural Systems
Stem Cell Models of Axial Patterning and Their Implications for V2a Neurons and Engineered Neural Systems
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153033
- ISBN
- 9798346877585
- DDC
- 574
- 저자명
- Elder, Nicholas.
- 서명/저자
- Stem Cell Models of Axial Patterning and Their Implications for V2a Neurons and Engineered Neural Systems
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 191 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Pollen, Alex.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약Human pluripotent stem cells have opened up unprecedented opportunities to model human development and disease. Critical to these models is differentiation of stem cells toward relevant cell identities. Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis formation and spinal cord development, but these processes cannot be interrogated directly in humans as they occur early post-implantation. However, this developmental period of regionalization significantly influences downstream cell fate. Here, I explore how models of axial patterning influence neural development and how these developmental models can influence engineered neural systems. First, I report an organoid model of neural tube extension derived from human pluripotent stem cell aggregates which recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Next, I investigate the effect of early progenitor regionalization on mature V2a interneurons which reside in the hindbrain and spinal cord. Using a multiomics approach, I identify lasting epigenetic and transcriptional differences as a result of early developmental regionalization. The epigenetic differences suggest that uniquely open regions of chromatin are accessed by different transcription factor families, while the differences in transcription point to differences in axonal extension and synapse formation. I also observe differences in spontaneous activity produced from regionally distinct neuron populations. Computational modeling and knockdown validation studies identify CREB5 and TCF7L2 as mediators of some of the region-specific differences in gene expression. Finally, I show that attempting to 'skip' developmental patterning by induced transcription factor expression yields a population unlike either developmentally relevant V2a population, highlighting the importance of following developmental steps in establishing cell identities in vitro. This observation leads me to explore ways to achieve cell type specificity by contrasting directed and induced differentiation strategies and proposing ways they can complement one another to better recapitulate target cell type identity.
- 일반주제명
- Developmental biology
- 일반주제명
- Cellular biology
- 일반주제명
- Neurosciences
- 키워드
- Axial elongation
- 키워드
- Axial patterning
- 키워드
- Cell engineering
- 키워드
- Human stem cell
- 키워드
- Regionalization
- 키워드
- V2a interneuron
- 기타저자
- University of California, San Francisco Developmental and Stem Cell Biology
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798346877585
■035 ▼a(MiAaPQ)AAI31636700
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aElder, Nicholas.▼0(orcid)0000-0003-0889-7687
■24510▼aStem Cell Models of Axial Patterning and Their Implications for V2a Neurons and Engineered Neural Systems
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a191 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Pollen, Alex.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aHuman pluripotent stem cells have opened up unprecedented opportunities to model human development and disease. Critical to these models is differentiation of stem cells toward relevant cell identities. Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis formation and spinal cord development, but these processes cannot be interrogated directly in humans as they occur early post-implantation. However, this developmental period of regionalization significantly influences downstream cell fate. Here, I explore how models of axial patterning influence neural development and how these developmental models can influence engineered neural systems. First, I report an organoid model of neural tube extension derived from human pluripotent stem cell aggregates which recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Next, I investigate the effect of early progenitor regionalization on mature V2a interneurons which reside in the hindbrain and spinal cord. Using a multiomics approach, I identify lasting epigenetic and transcriptional differences as a result of early developmental regionalization. The epigenetic differences suggest that uniquely open regions of chromatin are accessed by different transcription factor families, while the differences in transcription point to differences in axonal extension and synapse formation. I also observe differences in spontaneous activity produced from regionally distinct neuron populations. Computational modeling and knockdown validation studies identify CREB5 and TCF7L2 as mediators of some of the region-specific differences in gene expression. Finally, I show that attempting to 'skip' developmental patterning by induced transcription factor expression yields a population unlike either developmentally relevant V2a population, highlighting the importance of following developmental steps in establishing cell identities in vitro. This observation leads me to explore ways to achieve cell type specificity by contrasting directed and induced differentiation strategies and proposing ways they can complement one another to better recapitulate target cell type identity.
■590 ▼aSchool code: 0034.
■650 4▼aDevelopmental biology
■650 4▼aCellular biology
■650 4▼aNeurosciences
■653 ▼aAxial elongation
■653 ▼aAxial patterning
■653 ▼aCell engineering
■653 ▼aHuman stem cell
■653 ▼aRegionalization
■653 ▼aV2a interneuron
■690 ▼a0758
■690 ▼a0379
■690 ▼a0317
■71020▼aUniversity of California, San Francisco▼bDevelopmental and Stem Cell Biology.
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164699▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
