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Developmental Origins and Molecular Mechanisms of Sacrococcygeal Teratomas: Insights from Primordial Germ Cells, X-Chromosome Biology, and Epigenetic Reprogramming
Developmental Origins and Molecular Mechanisms of Sacrococcygeal Teratomas: Insights from Primordial Germ Cells, X-Chromosome Biology, and Epigenetic Reprogramming
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105259
- ISBN
- 9798270227586
- DDC
- 574
- 서명/저자
- Developmental Origins and Molecular Mechanisms of Sacrococcygeal Teratomas: Insights from Primordial Germ Cells, X-Chromosome Biology, and Epigenetic Reprogramming
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 296 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Laird, Diana;Panning, Barbara.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Sacrococcygeal teratomas (SCTs) are the most common neonatal tumors, yet their developmental origins, molecular mechanisms, and female-sex bias remain poorly understood. This thesis integrates spatial transcriptomics, single-cell RNA sequencing, and experimental models to investigate SCT biology and its hypothesized origins from primordial germ cells (PGCs). We first examined female primate ovarian reserve establishment, showing that rhesus macaque primordial follicles arise from two pre-granulosa cell subtypes, with PG2 cells predominating and supporting early hormone production before birth. We then generated a cellular atlas of SCTs, revealing epithelia-rich and epithelia-poor subtypes, marked inter-tumor heterogeneity, and evidence that X-chromosome inactivation failure in female tumors may contribute to observed sex biases. Finally, using iPSC-derived PGC-like cells, we modeled germ cell reprogramming to pluripotency, identifying transcriptional, metabolic, and epigenetic remodeling events, including DNMT3B-mediated DNA methylation. We also initiated development of a dual SOX2-SOX17 reporter system to follow this process and explored hindgut organoid co-cultures and fetal mouse injections as potential platforms to study environmental influences on germ cell fate. Together, these studies provide insights into fetal ovarian development, highlight sources of heterogeneity in SCTs, and suggest possible mechanisms by which germ cell reprogramming could contribute to tumor origins.
- 일반주제명
- Developmental biology
- 일반주제명
- Oncology
- 일반주제명
- Medicine
- 일반주제명
- Cellular biology
- 키워드
- Pluripotency
- 기타저자
- University of California, San Francisco Developmental and Stem Cell Biology
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798270227586
■035 ▼a(MiAaPQ)AAI32280207
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aRojas, Ernesto Javier.
■24510▼aDevelopmental Origins and Molecular Mechanisms of Sacrococcygeal Teratomas: Insights from Primordial Germ Cells, X-Chromosome Biology, and Epigenetic Reprogramming
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a296 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Laird, Diana;Panning, Barbara.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aSacrococcygeal teratomas (SCTs) are the most common neonatal tumors, yet their developmental origins, molecular mechanisms, and female-sex bias remain poorly understood. This thesis integrates spatial transcriptomics, single-cell RNA sequencing, and experimental models to investigate SCT biology and its hypothesized origins from primordial germ cells (PGCs). We first examined female primate ovarian reserve establishment, showing that rhesus macaque primordial follicles arise from two pre-granulosa cell subtypes, with PG2 cells predominating and supporting early hormone production before birth. We then generated a cellular atlas of SCTs, revealing epithelia-rich and epithelia-poor subtypes, marked inter-tumor heterogeneity, and evidence that X-chromosome inactivation failure in female tumors may contribute to observed sex biases. Finally, using iPSC-derived PGC-like cells, we modeled germ cell reprogramming to pluripotency, identifying transcriptional, metabolic, and epigenetic remodeling events, including DNMT3B-mediated DNA methylation. We also initiated development of a dual SOX2-SOX17 reporter system to follow this process and explored hindgut organoid co-cultures and fetal mouse injections as potential platforms to study environmental influences on germ cell fate. Together, these studies provide insights into fetal ovarian development, highlight sources of heterogeneity in SCTs, and suggest possible mechanisms by which germ cell reprogramming could contribute to tumor origins.
■590 ▼aSchool code: 0034.
■650 4▼aDevelopmental biology
■650 4▼aOncology
■650 4▼aMedicine
■650 4▼aCellular biology
■653 ▼aEmbryonic germ cells
■653 ▼aPluripotency
■653 ▼aSacrococcygeal teratomas
■653 ▼aSpatial transcriptomics
■653 ▼aX-chromosome inactivation
■690 ▼a0758
■690 ▼a0992
■690 ▼a0564
■690 ▼a0379
■71020▼aUniversity of California, San Francisco▼bDevelopmental and Stem Cell Biology.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360067▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
