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Mapping Lineage Dynamics of Progenitors in the Human Cerebral Cortex
Mapping Lineage Dynamics of Progenitors in the Human Cerebral Cortex
Mapping Lineage Dynamics of Progenitors in the Human Cerebral Cortex

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151332
ISBN  
9798382814810
DDC  
574
저자명  
Keefe, Matthew George.
서명/저자  
Mapping Lineage Dynamics of Progenitors in the Human Cerebral Cortex
발행사항  
[Sl] : University of California, San Francisco, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
156 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
주기사항  
Advisor: Wagner, Daniel.
학위논문주기  
Thesis (Ph.D.)--University of California, San Francisco, 2024.
초록/해제  
요약During development of the cerebral cortex, progenitors give rise to diverse cell types in a spatially and temporally defined fashion, but the fate competence of individual progenitors and the lineage relationships between mature cell types has been difficult to ascertain. In this dissertation, I apply a novel prospective lineage tracing tool utilizing synthetic DNA barcodes to label human cortical progenitors and their resulting daughter cells in order to profile their output throughout neurogenesis. First, I show that cortical progenitors are capable to produce inhibitory interneurons, a cell type that had previously been widely believed to derive only from the ventral ganglionic eminences. In an in vitro model as well as in a xenotransplantation model, individual progenitors give rise to both excitatory and inhibitory neurons. Next, I extend this approach to more thoroughly analyze the temporal dynamics of cortical neurogenesis. Lineage tracing across the late second trimester reveals that inhibitory neurogenesis from dorsal progenitors is not a constant feature of cortical development, but arises prominently after midgestation. Furthermore, I show that excitatory neurogenesis proceeds at the ventricular zone throughout development, particularly by a subset of radial glia known as truncated radial glia. These excitatory neurons include neurons of deep layer identity, which are born throughout the second trimester, not just at early timepoints as had been previously believed. Together, these results shed light on previously unappreciated aspects of human cortical neurogenesis and highlight the diverse lineage potential of individual cortical progenitors.
일반주제명  
Developmental biology
일반주제명  
Neurosciences
일반주제명  
Cellular biology
키워드  
Cerebral cortex
키워드  
Cortical development
키워드  
Lineage tracing
키워드  
Progenitors
키워드  
Radial glia
기타저자  
University of California, San Francisco Developmental and Stem Cell Biology
기본자료저록  
Dissertations Abstracts International. 85-12B.
전자적 위치 및 접속  
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■020    ▼a9798382814810
■035    ▼a(MiAaPQ)AAI31241346
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aKeefe,  Matthew  George.▼0(orcid)0000-0002-2477-2975
■24510▼aMapping  Lineage  Dynamics  of  Progenitors  in  the  Human  Cerebral  Cortex
■260    ▼a[Sl]▼bUniversity  of  California,  San  Francisco▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a156  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-12,  Section:  B.
■500    ▼aAdvisor:  Wagner,  Daniel.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  San  Francisco,  2024.
■520    ▼aDuring  development  of  the  cerebral  cortex,  progenitors  give  rise  to  diverse  cell  types  in  a  spatially  and  temporally  defined  fashion,  but  the  fate  competence  of  individual  progenitors  and  the  lineage  relationships  between  mature  cell  types  has  been  difficult  to  ascertain.  In  this  dissertation,  I  apply  a  novel  prospective  lineage  tracing  tool  utilizing  synthetic  DNA  barcodes  to  label  human  cortical  progenitors  and  their  resulting  daughter  cells  in  order  to  profile  their  output  throughout  neurogenesis.  First,  I  show  that  cortical  progenitors  are  capable  to  produce  inhibitory  interneurons,  a  cell  type  that  had  previously  been  widely  believed  to  derive  only  from  the  ventral  ganglionic  eminences.  In  an  in  vitro  model  as  well  as  in  a  xenotransplantation  model,  individual  progenitors  give  rise  to  both  excitatory  and  inhibitory  neurons.  Next,  I  extend  this  approach  to  more  thoroughly  analyze  the  temporal  dynamics  of  cortical  neurogenesis.  Lineage  tracing  across  the  late  second  trimester  reveals  that  inhibitory  neurogenesis  from  dorsal  progenitors  is  not  a  constant  feature  of  cortical  development,  but  arises  prominently  after  midgestation.  Furthermore,  I  show  that  excitatory  neurogenesis  proceeds  at  the  ventricular  zone  throughout  development,  particularly  by  a  subset  of  radial  glia  known  as  truncated  radial  glia.  These  excitatory  neurons  include  neurons  of  deep  layer  identity,  which  are  born  throughout  the  second  trimester,  not  just  at  early  timepoints  as  had  been  previously  believed.  Together,  these  results  shed  light  on  previously  unappreciated  aspects  of  human  cortical  neurogenesis  and  highlight  the  diverse  lineage  potential  of  individual  cortical  progenitors.
■590    ▼aSchool  code:  0034.
■650  4▼aDevelopmental  biology
■650  4▼aNeurosciences
■650  4▼aCellular  biology
■653    ▼aCerebral  cortex
■653    ▼aCortical  development
■653    ▼aLineage  tracing
■653    ▼aProgenitors
■653    ▼aRadial  glia
■690    ▼a0758
■690    ▼a0317
■690    ▼a0379
■71020▼aUniversity  of  California,  San  Francisco▼bDevelopmental  and  Stem  Cell  Biology.
■7730  ▼tDissertations  Abstracts  International▼g85-12B.
■790    ▼a0034
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161271▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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