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Generating Exogenic Neural Cells Through Blastocyst Complementation for Neurodegenerative Diseases
Generating Exogenic Neural Cells Through Blastocyst Complementation for Neurodegenerative Diseases
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103535
- ISBN
- 9798286444526
- DDC
- 616
- 저자명
- Strell, Phoebe.
- 서명/저자
- Generating Exogenic Neural Cells Through Blastocyst Complementation for Neurodegenerative Diseases
- 발행사항
- [Sl] : University of Minnesota, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 215 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Low, Walter C.
- 학위논문주기
- Thesis (Ph.D.)--University of Minnesota, 2025.
- 초록/해제
- 요약Neurodegenerative diseases burden individuals, their families, and the economy. The progressive symptoms and neuropathology affect cognitive skills and daily activities. The only available treatments alleviate symptoms, but do not stop or change the course of disease progression. Therapeutics are rather limited for neurodegenerative diseases. Cellular transplantation to treat neurodegenerative diseases has shown promise as a therapeutic, but a novel source of cells is needed. Fetal/embryonic tissue is fraught with ethical concerns and many stem cell derived cells behave differently than primary cell types. This dissertation seeks to bridge some of these gaps by characterizing and quantifying cell types found within chimeric brains. Insights from this research have the potential to inform neurodegenerative therapeutics, deliver new information of cell survival and differentiation, and elucidate some interspecies chimeric differences.We reviewed the current state of cellular transplantation, relevant therapeutic neuronal and non-neuronal types, interspecies chimeric barriers, intraspecies and interspecies chimeras, and generation of chimeric brains. Our study of E12.5 intraspecies mouse-mouse chimeric brains identified, characterized, and quantified serotonergic, dopaminergic, and cholinergic precursors derived from donor cells. Microglia-like and macrophage-like cells derived from donor cells were also observed and quantified. To better understand development of these cells, E16.5 intraspecies mouse-mouse chimeric brains were generated. To support interspecies chimera characterization, we generated E12.5 interspecies rat-mouse chimeric brains, and began to characterize and quantify cell types. Dopaminergic precursors, microglia-like and macrophage-like cells were identified cells in these interspecies chimeras. To demonstrate that a targeted developmental niche could be made, we developed and tested single guide RNA to target a PU.1 gene that is important for microglia development.This research seeks to improve our understanding of cell types and proportions of those cell types generated in wild type intraspecies and interspecies chimeras. It also highlights new methods, like automated imaging, for quantifying cell types within these chimeric animals. This research also provides the foundational steps for making a new PU.1 knockout model to be used with blastocyst complementation.
- 일반주제명
- Neurosciences
- 일반주제명
- Cellular biology
- 일반주제명
- Pathology
- 일반주제명
- Molecular biology
- 키워드
- Neuropathology
- 키워드
- Cognitive skills
- 기타저자
- University of Minnesota Comparative and Molecular Biosciences
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798286444526
■035 ▼a(MiAaPQ)AAI32040387
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aStrell, Phoebe.
■24510▼aGenerating Exogenic Neural Cells Through Blastocyst Complementation for Neurodegenerative Diseases
■260 ▼a[Sl]▼bUniversity of Minnesota▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a215 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Low, Walter C.
■5021 ▼aThesis (Ph.D.)--University of Minnesota, 2025.
■520 ▼aNeurodegenerative diseases burden individuals, their families, and the economy. The progressive symptoms and neuropathology affect cognitive skills and daily activities. The only available treatments alleviate symptoms, but do not stop or change the course of disease progression. Therapeutics are rather limited for neurodegenerative diseases. Cellular transplantation to treat neurodegenerative diseases has shown promise as a therapeutic, but a novel source of cells is needed. Fetal/embryonic tissue is fraught with ethical concerns and many stem cell derived cells behave differently than primary cell types. This dissertation seeks to bridge some of these gaps by characterizing and quantifying cell types found within chimeric brains. Insights from this research have the potential to inform neurodegenerative therapeutics, deliver new information of cell survival and differentiation, and elucidate some interspecies chimeric differences.We reviewed the current state of cellular transplantation, relevant therapeutic neuronal and non-neuronal types, interspecies chimeric barriers, intraspecies and interspecies chimeras, and generation of chimeric brains. Our study of E12.5 intraspecies mouse-mouse chimeric brains identified, characterized, and quantified serotonergic, dopaminergic, and cholinergic precursors derived from donor cells. Microglia-like and macrophage-like cells derived from donor cells were also observed and quantified. To better understand development of these cells, E16.5 intraspecies mouse-mouse chimeric brains were generated. To support interspecies chimera characterization, we generated E12.5 interspecies rat-mouse chimeric brains, and began to characterize and quantify cell types. Dopaminergic precursors, microglia-like and macrophage-like cells were identified cells in these interspecies chimeras. To demonstrate that a targeted developmental niche could be made, we developed and tested single guide RNA to target a PU.1 gene that is important for microglia development.This research seeks to improve our understanding of cell types and proportions of those cell types generated in wild type intraspecies and interspecies chimeras. It also highlights new methods, like automated imaging, for quantifying cell types within these chimeric animals. This research also provides the foundational steps for making a new PU.1 knockout model to be used with blastocyst complementation.
■590 ▼aSchool code: 0130.
■650 4▼aNeurosciences
■650 4▼aCellular biology
■650 4▼aPathology
■650 4▼aMolecular biology
■653 ▼aNeurodegenerative diseases
■653 ▼aNeuropathology
■653 ▼aNeurodegenerative therapeutics
■653 ▼aCellular transplantation
■653 ▼aCognitive skills
■690 ▼a0317
■690 ▼a0379
■690 ▼a0307
■690 ▼a0571
■71020▼aUniversity of Minnesota▼bComparative and Molecular Biosciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0130
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357604▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
