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Dissecting Mechanisms of Immune Self-Tolerance via Bioinformatic Analysis of Cellular and Molecular States
Dissecting Mechanisms of Immune Self-Tolerance via Bioinformatic Analysis of Cellular and Molecular States
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105254
- ISBN
- 9798270227210
- DDC
- 616.079
- 저자명
- Germino, Joe.
- 서명/저자
- Dissecting Mechanisms of Immune Self-Tolerance via Bioinformatic Analysis of Cellular and Molecular States
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 110 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Gardner, James;Anderson, Mark.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Multicellular organisms rely on complex immune systems that initiate innate and adaptive responses to invading pathogens to survive. A crucial challenge for adaptive immunity is distinguishing self from invading non-self. For T cells, this self-education is established through central tolerance in the thymus, mediated largely by Aire-expressing medullary thymic epithelial cells (mTECs), and is reinforced through peripheral tolerance in the host's tissues. While some aspects of central tolerance are well characterized, peripheral tolerance remains less well-defined; however recent work implicates an MHCII expressing, RORgt⁺ antigen-presenting cell in tolerance to food antigens and the gut microbiome. Because of the complexity of these tolerance mechanisms and the cellular diversity of their mediators, integrative bioinformatic analyses of large multi-modal 'omics datasets can provide key insights to help unravel these biological processes. Using single-cell transcriptomics to investigate mouse models of central tolerance, we identified a novel role for the transcription factor Fezf2 in regulating a Stat3-dependent developmental switch between mTEC self-renewal and terminal differentiation, with important implications for age-associated thymic atrophy. We also developed a computational method to optimize deep mutational scan (DMS) experimental design that could be used for high-throughput screening of individual mutations' effects on protein functions related to immune tolerance. Finally, we adapted a single-cell ATAC-sequencing method for detecting intracellular bacteria in individual antigen-presenting cells, with potentially useful applications in studying the APCs responsible for self-tolerance to the gut microbiome.
- 일반주제명
- Immunology
- 일반주제명
- Computer science
- 일반주제명
- Microbiology
- 일반주제명
- Biomedical engineering
- 일반주제명
- Bioinformatics
- 키워드
- Immune tolerance
- 기타저자
- University of California, San Francisco Biomedical Sciences
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202105254
■006m o d
■007cr#unu||||||||
■020 ▼a9798270227210
■035 ▼a(MiAaPQ)AAI32277590
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aGermino, Joe.
■24510▼aDissecting Mechanisms of Immune Self-Tolerance via Bioinformatic Analysis of Cellular and Molecular States
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a110 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Gardner, James;Anderson, Mark.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aMulticellular organisms rely on complex immune systems that initiate innate and adaptive responses to invading pathogens to survive. A crucial challenge for adaptive immunity is distinguishing self from invading non-self. For T cells, this self-education is established through central tolerance in the thymus, mediated largely by Aire-expressing medullary thymic epithelial cells (mTECs), and is reinforced through peripheral tolerance in the host's tissues. While some aspects of central tolerance are well characterized, peripheral tolerance remains less well-defined; however recent work implicates an MHCII expressing, RORgt⁺ antigen-presenting cell in tolerance to food antigens and the gut microbiome. Because of the complexity of these tolerance mechanisms and the cellular diversity of their mediators, integrative bioinformatic analyses of large multi-modal 'omics datasets can provide key insights to help unravel these biological processes. Using single-cell transcriptomics to investigate mouse models of central tolerance, we identified a novel role for the transcription factor Fezf2 in regulating a Stat3-dependent developmental switch between mTEC self-renewal and terminal differentiation, with important implications for age-associated thymic atrophy. We also developed a computational method to optimize deep mutational scan (DMS) experimental design that could be used for high-throughput screening of individual mutations' effects on protein functions related to immune tolerance. Finally, we adapted a single-cell ATAC-sequencing method for detecting intracellular bacteria in individual antigen-presenting cells, with potentially useful applications in studying the APCs responsible for self-tolerance to the gut microbiome.
■590 ▼aSchool code: 0034.
■650 4▼aImmunology
■650 4▼aComputer science
■650 4▼aMicrobiology
■650 4▼aBiomedical engineering
■650 4▼aBioinformatics
■653 ▼aImmune tolerance
■653 ▼aProtein language models
■653 ▼aThymic epithelial cells
■653 ▼aMulticellular organisms
■653 ▼aDeep mutational scan
■690 ▼a0982
■690 ▼a0984
■690 ▼a0541
■690 ▼a0410
■690 ▼a0715
■71020▼aUniversity of California, San Francisco▼bBiomedical Sciences.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360033▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
