Advanced

Molecular specification of expanded forebrain neural stem and progenitor cells

Parmar, Malin LU (2003)
Abstract (Swedish)
Popular Abstract in Swedish

Hjärnan är ett komplext system, som är uppbyggd av många olika sorters celler. Alla dessa celler har sitt ursprung i en speciell typ av cell, stamcellen. Neurala stamceller är omogna celler som har förmågan att genom delning både föröka sig själva genom att bilda fler stamceller, och ge upphov till de olika mogna celltyper som finns i hjärnan. Mycket av intresset för dessa celler kommer från förhoppningen om att de i framtiden ska kunna användas för att bota sjukdomar i hjärnan, såsom Parkinsons sjukdom. Eftersom stamceller har förmågan att dela sig och bli fler kan man plocka ut dem från hjärnan och odla dem i cellkultur. På så sätt ökar man antalet stamceller (expansion), som sedan kan... (More)
Popular Abstract in Swedish

Hjärnan är ett komplext system, som är uppbyggd av många olika sorters celler. Alla dessa celler har sitt ursprung i en speciell typ av cell, stamcellen. Neurala stamceller är omogna celler som har förmågan att genom delning både föröka sig själva genom att bilda fler stamceller, och ge upphov till de olika mogna celltyper som finns i hjärnan. Mycket av intresset för dessa celler kommer från förhoppningen om att de i framtiden ska kunna användas för att bota sjukdomar i hjärnan, såsom Parkinsons sjukdom. Eftersom stamceller har förmågan att dela sig och bli fler kan man plocka ut dem från hjärnan och odla dem i cellkultur. På så sätt ökar man antalet stamceller (expansion), som sedan kan producera nya nervceller Hur vet då den nya nevcellen vilken typ av cell den ska bli? Har stamcellerna bibehållit den information som krävs för att bilda “rätt” sorts nervcell? Det är dessa frågor som jag har försökt svara på i mitt avhandlingsarbete. För att studera detta har jag isolerat stamceller från olika områden i hjärnan och sedan expanderat dem i cellkultur. När cellerna delat sig många gånger och blivit tusentals fler, har jag studerat uttrycket av gener och proteiner som är karakteristiska för stamcellerna i ursprungsområdena. På så sätt har jag kunnat visa att de celler som delat sig utanför hjärnan är väldigt lika de celler som delat sig inne i hjärnan. Cellerna har alltså behållt ett mine av det område i hjärnan som de plockades ut från, och beroende på var de kommer ifrån ger de upphov till olika sorters nervceller. (Less)
Abstract
The molecular specification of neural precursor cells has been suggested to be a progressive process, with a transition from an early requirement for extrinsic signals to intrinsic mechanisms. Thus, the cells in the nervous system acquire distinct fates in response to extrinsic signals, which activate repertoires of transcription factors in a region and cell type specific manner. The studies in this thesis are aimed to increase our understanding as to the extent neural stem and progenitor cells maintain their regional identity during expansion in vitro. To address this issue, cells isolated from different regions of the embryonic or adult mouse and human forebrain were expanded, either as free-floating neurosphere cultures or as attached... (More)
The molecular specification of neural precursor cells has been suggested to be a progressive process, with a transition from an early requirement for extrinsic signals to intrinsic mechanisms. Thus, the cells in the nervous system acquire distinct fates in response to extrinsic signals, which activate repertoires of transcription factors in a region and cell type specific manner. The studies in this thesis are aimed to increase our understanding as to the extent neural stem and progenitor cells maintain their regional identity during expansion in vitro. To address this issue, cells isolated from different regions of the embryonic or adult mouse and human forebrain were expanded, either as free-floating neurosphere cultures or as attached monolayer cultures. The expression of developmental control genes specific for each region was analyzed in the expanded cells, and their developmental potency was tested both after in vitro differentiation, and after transplantation in vivo. The results show that independent of culture method the expanded cells maintain many aspects of their regional identity. They express developmental control genes characteristic for their area of origin, and upon differentiation they generate neurons characteristic of that area. However, the different culture methods differentially expand specific progenitor populations within each area, and the progenitor composition in the cultures is decisive for the differentiation potential of the expanded cells. Besides its relevance for understanding basic developmental processes, the results may also have an impact on the selection of donor cells and expansion method for cells to be used in cell replacement therapies (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Prof. van der Kooy, Derek
organization
publishing date
type
Thesis
publication status
published
subject
keywords
teratology, ontogeny, embryology (human), Development biology, developmental control genes, in vitro expansion, transplantation, precursor cell, stem cells, progenitor cell, human, mouse, Utvecklingsbiologi, teratologi, embryologi (människa)
pages
160 pages
publisher
Malin Parmar, BMC A11, 221 84 LUND,
defense location
Segerfalksalen, Wallenberg Neurocenter
defense date
2003-09-03 10:15
ISBN
91-628-5756-8
language
English
LU publication?
yes
id
8cb0cf57-defe-409e-b927-fcdfc01fe817 (old id 466002)
date added to LUP
2007-09-27 16:07:21
date last changed
2016-09-19 08:45:08
@misc{8cb0cf57-defe-409e-b927-fcdfc01fe817,
  abstract     = {The molecular specification of neural precursor cells has been suggested to be a progressive process, with a transition from an early requirement for extrinsic signals to intrinsic mechanisms. Thus, the cells in the nervous system acquire distinct fates in response to extrinsic signals, which activate repertoires of transcription factors in a region and cell type specific manner. The studies in this thesis are aimed to increase our understanding as to the extent neural stem and progenitor cells maintain their regional identity during expansion in vitro. To address this issue, cells isolated from different regions of the embryonic or adult mouse and human forebrain were expanded, either as free-floating neurosphere cultures or as attached monolayer cultures. The expression of developmental control genes specific for each region was analyzed in the expanded cells, and their developmental potency was tested both after in vitro differentiation, and after transplantation in vivo. The results show that independent of culture method the expanded cells maintain many aspects of their regional identity. They express developmental control genes characteristic for their area of origin, and upon differentiation they generate neurons characteristic of that area. However, the different culture methods differentially expand specific progenitor populations within each area, and the progenitor composition in the cultures is decisive for the differentiation potential of the expanded cells. Besides its relevance for understanding basic developmental processes, the results may also have an impact on the selection of donor cells and expansion method for cells to be used in cell replacement therapies},
  author       = {Parmar, Malin},
  isbn         = {91-628-5756-8},
  keyword      = {teratology,ontogeny,embryology (human),Development biology,developmental control genes,in vitro expansion,transplantation,precursor cell,stem cells,progenitor cell,human,mouse,Utvecklingsbiologi,teratologi,embryologi (människa)},
  language     = {eng},
  pages        = {160},
  publisher    = {ARRAY(0xc000690)},
  title        = {Molecular specification of expanded forebrain neural stem and progenitor cells},
  year         = {2003},
}