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Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development
Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogenei...
Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105304
ISBN  
9798270226480
DDC  
574
저자명  
Wedderburn-Pugh, Kaylee.
서명/저자  
Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development
발행사항  
[Sl] : University of California, San Francisco, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
163 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
주기사항  
Advisor: MacKenzie, Tippi C.;Paredes, Mercedes F.
학위논문주기  
Thesis (Ph.D.)--University of California, San Francisco, 2025.
초록/해제  
요약The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) regulate exchange between the peripheral circulation and the central nervous system (CNS). During development, these barriers have a selective permeability that differs from adult states, creating both vulnerabilities and therapeutic opportunities. This dissertation addresses fundamental questions about blood-CNS barrier during development. (1) What endothelial and mural cell subtypes are present during early CNS vascular development? (2) How do these subtypes map to regions of differing barrier permeability? (3) What molecular signatures distinguish these regions? Chapter 2 presents a single-cell atlas of mouse brain and spinal cord vasculature at embryonic day (E)13.5 and E18.5, identifying endothelial and mural subtypes that establish arteriovenous zonation. Trajectory analysis revealed maturation programs progressing from proliferation through angiogenesis to transporter-rich barrier states, with region-specific signatures distinguishing brain from spinal cord. Chapter 3 developed a "BBB scorecard" quantifying CNS-specific signatures. Combined with permeability mapping and RNA in situ hybridization, permeable zones align with specific vascular subtypes. Col15a1 was identified as a potential marker of permeable territories. Chapter 4 investigated immune-vascular interactions, identifying galectin-9 as a potential mediator and CD206+ macrophages in multiple positions relative to vessels, consistent with transmigration. These findings establish underscore vascular subtype composition and regional specialization in blood-CNS barrier function.
일반주제명  
Developmental biology
일반주제명  
Cellular biology
일반주제명  
Neurosciences
키워드  
Blood-brain barrier
키워드  
Blood-spinal cord barrier
키워드  
Neurovasculature
키워드  
Central nervous system
키워드  
Mouse brain
기타저자  
University of California, San Francisco Biomedical Sciences
기본자료저록  
Dissertations Abstracts International. 87-06B.
전자적 위치 및 접속  
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MARC

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■035    ▼a(MiAaPQ)AAI32282827
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aWedderburn-Pugh,  Kaylee.
■24510▼aCellular  and  Molecular  Mechanisms  of  Blood-Brain  and  Blood-Spinal  Cord  Barrier  Heterogeneity  During  Development
■260    ▼a[Sl]▼bUniversity  of  California,  San  Francisco▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a163  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-06,  Section:  B.
■500    ▼aAdvisor:  MacKenzie,  Tippi  C.;Paredes,  Mercedes  F.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  San  Francisco,  2025.
■520    ▼aThe  blood-brain  barrier  (BBB)  and  blood-spinal  cord  barrier  (BSCB)  regulate  exchange  between  the  peripheral  circulation  and  the  central  nervous  system  (CNS).  During  development,  these  barriers  have  a  selective  permeability  that  differs  from  adult  states,  creating  both  vulnerabilities  and  therapeutic  opportunities.  This  dissertation  addresses  fundamental  questions  about  blood-CNS  barrier  during  development.  (1)  What  endothelial  and  mural  cell  subtypes  are  present  during  early  CNS  vascular  development?  (2)  How  do  these  subtypes  map  to  regions  of  differing  barrier  permeability?  (3)  What  molecular  signatures  distinguish  these  regions?  Chapter  2  presents  a  single-cell  atlas  of  mouse  brain  and  spinal  cord  vasculature  at  embryonic  day  (E)13.5  and  E18.5,  identifying  endothelial  and  mural  subtypes  that  establish  arteriovenous  zonation.  Trajectory  analysis  revealed  maturation  programs  progressing  from  proliferation  through  angiogenesis  to  transporter-rich  barrier  states,  with  region-specific  signatures  distinguishing  brain  from  spinal  cord.  Chapter  3  developed  a  "BBB  scorecard"  quantifying  CNS-specific  signatures.  Combined  with  permeability  mapping  and  RNA  in  situ  hybridization,  permeable  zones  align  with  specific  vascular  subtypes.  Col15a1  was  identified  as  a  potential  marker  of  permeable  territories.  Chapter  4  investigated  immune-vascular  interactions,  identifying  galectin-9  as  a  potential  mediator  and  CD206+  macrophages  in  multiple  positions  relative  to  vessels,  consistent  with  transmigration.  These  findings  establish  underscore  vascular  subtype  composition  and  regional  specialization  in  blood-CNS  barrier  function.
■590    ▼aSchool  code:  0034.
■650  4▼aDevelopmental  biology
■650  4▼aCellular  biology
■650  4▼aNeurosciences
■653    ▼aBlood-brain  barrier
■653    ▼aBlood-spinal  cord  barrier
■653    ▼aNeurovasculature
■653    ▼aCentral  nervous  system
■653    ▼aMouse  brain
■690    ▼a0758
■690    ▼a0379
■690    ▼a0317
■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=T17360103▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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