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Computational Approaches to Reprogram Neuronal Cell Identities in Ciona intestinalis- [electronic resource]
Computational Approaches to Reprogram Neuronal Cell Identities in Ciona intestinalis- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100439
- ISBN
- 9798379718503
- DDC
- 574
- 서명/저자
- Computational Approaches to Reprogram Neuronal Cell Identities in Ciona intestinalis - [electronic resource]
- 발행사항
- [S.l.]: : Princeton University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(177 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Levine, Michael S.;Singh, Mona.
- 학위논문주기
- Thesis (Ph.D.)--Princeton University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Understanding cell type identity and what determines cell fate, are fundamental to understanding the basic units of life, from which the complexities of organisms arise and evolve. A powerful application of this knowledge is in the field of reprogramming, in which we attempt to convert one cell type into another. Beyond understanding these foundational biological principles, we can further our success in regenerative medicine, in which damaged tissues and organs can be replaced by first reprogramming their constituent cell types. In this dissertation, I explore questions of cell type identity and reprogramming in neural cell types in Ciona intestinalis, the invertebrate closest evolutionarily to vertebrates.In Chapter 2, I begin by uncovering the effects of misexpressing the transcription factor POU IV, a homolog of Brn3 in vertebrates, on the specification of sensory cell types. I find that the epidermal cells are transformed into BTN/PSC "hybrids", or cells that predominantly exhibit properties of both BTNs and PSCs, due to ectopic coexpression of Neurogenin and Foxg that is triggered by an unexpected POU IV feedback loop. In Chapter 3, I focus on how to reliably reprogram neural cell types. I develop a computational framework, Circe, that predicts Cocktails, or combinations of transcription factors that can induce a given cell type when misexpressed. Circe is based on the premise that Cocktail transcription factors will be those that specify a cell type, and identifies them by analyzing a lineage tree reconstructed from single-cell data derived from all developmental stages in Ciona. I also present experimental evidence for the reprogramming of pigment and dorsal nerve cord cells into Bipolar Tail Neurons (BTNs).Finally, in Chapter 3, I turn my attention to the effects of Nodal signaling on the specification of neurons and embryonic patterning in Ciona. I recapitulated past findings and suggested new roles for Nodal, namely, a Nodal-mediated tradeoff between Nervous System (b) and Epidermal (b) Lineages, a Nodal signal at the 110-cell stage that is responsible for the specification of both pigment and Prop+ cells, and a "Fate Map Correction" between the 110-cell and Initial Tailbud stages.Taken together, this dissertation presents novel computational analyses and methods that further our understanding of how cell types are specified, defined, and reprogrammed.
- 일반주제명
- Bioinformatics.
- 일반주제명
- Developmental biology.
- 일반주제명
- Molecular biology.
- 일반주제명
- Molecular chemistry.
- 키워드
- Reprogramming
- 키워드
- Cell type
- 키워드
- Nodal signaling
- 키워드
- Circe
- 기타저자
- Princeton University Quantitative Computational Biology
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008240612s2023 us |||||||||||||||c||eng d■001000016932290
■00520240214100439
■006m o d
■007cr#unu||||||||
■020 ▼a9798379718503
■035 ▼a(MiAaPQ)AAI30491016
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aChacha, Prakriti Paul.
■24510▼aComputational Approaches to Reprogram Neuronal Cell Identities in Ciona intestinalis▼h[electronic resource]
■260 ▼a[S.l.]:▼bPrinceton University. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(177 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 84-12, Section: B.
■500 ▼aAdvisor: Levine, Michael S.;Singh, Mona.
■5021 ▼aThesis (Ph.D.)--Princeton University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aUnderstanding cell type identity and what determines cell fate, are fundamental to understanding the basic units of life, from which the complexities of organisms arise and evolve. A powerful application of this knowledge is in the field of reprogramming, in which we attempt to convert one cell type into another. Beyond understanding these foundational biological principles, we can further our success in regenerative medicine, in which damaged tissues and organs can be replaced by first reprogramming their constituent cell types. In this dissertation, I explore questions of cell type identity and reprogramming in neural cell types in Ciona intestinalis, the invertebrate closest evolutionarily to vertebrates.In Chapter 2, I begin by uncovering the effects of misexpressing the transcription factor POU IV, a homolog of Brn3 in vertebrates, on the specification of sensory cell types. I find that the epidermal cells are transformed into BTN/PSC "hybrids", or cells that predominantly exhibit properties of both BTNs and PSCs, due to ectopic coexpression of Neurogenin and Foxg that is triggered by an unexpected POU IV feedback loop. In Chapter 3, I focus on how to reliably reprogram neural cell types. I develop a computational framework, Circe, that predicts Cocktails, or combinations of transcription factors that can induce a given cell type when misexpressed. Circe is based on the premise that Cocktail transcription factors will be those that specify a cell type, and identifies them by analyzing a lineage tree reconstructed from single-cell data derived from all developmental stages in Ciona. I also present experimental evidence for the reprogramming of pigment and dorsal nerve cord cells into Bipolar Tail Neurons (BTNs).Finally, in Chapter 3, I turn my attention to the effects of Nodal signaling on the specification of neurons and embryonic patterning in Ciona. I recapitulated past findings and suggested new roles for Nodal, namely, a Nodal-mediated tradeoff between Nervous System (b) and Epidermal (b) Lineages, a Nodal signal at the 110-cell stage that is responsible for the specification of both pigment and Prop+ cells, and a "Fate Map Correction" between the 110-cell and Initial Tailbud stages.Taken together, this dissertation presents novel computational analyses and methods that further our understanding of how cell types are specified, defined, and reprogrammed.
■590 ▼aSchool code: 0181.
■650 4▼aBioinformatics.
■650 4▼aDevelopmental biology.
■650 4▼aMolecular biology.
■650 4▼aMolecular chemistry.
■653 ▼aCellular identity
■653 ▼aReprogramming
■653 ▼aCell type
■653 ▼aCiona intestinalis
■653 ▼aTranscription factor
■653 ▼aNodal signaling
■653 ▼aCirce
■690 ▼a0715
■690 ▼a0758
■690 ▼a0431
■690 ▼a0307
■71020▼aPrinceton University▼bQuantitative Computational Biology.
■7730 ▼tDissertations Abstracts International▼g84-12B.
■773 ▼tDissertation Abstract International
■790 ▼a0181
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16932290▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
