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Neural Stem Cells in the Central Ner...

Xu, Wenjun.

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Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and Lineage Relationship.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and Lineage Relationship./
作者:	Xu, Wenjun.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
面頁冊數:	220 p.
附註:	Source: Dissertation Abstracts International, Volume: 79-03(E), Section: B.
Contained By:	Dissertation Abstracts International79-03B(E).
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10603840
ISBN:	9780355530858

Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and Lineage Relationship.
Xu, Wenjun.

Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and Lineage Relationship. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 220 p.

Source: Dissertation Abstracts International, Volume: 79-03(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2017.

Adult neural stem cells (NSC) reside in the periventricular region along the entire neuaxis. It is thought that a subset of mature astrocytes, expressing glial fibrillary acidic protein (GFAP), known as definitive NSCs (dNSC) are responsible for neurogenesis within the adult forebrain. We have identified a novel population of a rare, primitive NSC (pNSC) expressing low level of the pluripotency marker, Oct4. Both dNSC and pNSC can be isolated in vitro using neurosphere assays and differentiate into glial and neuronal cell types. Transplantation studies of pure pNSCs into the anterior rostral migratory stream of mice produced migrating neuroblasts and neurons in the olfactory bulb suggesting a potential lineage relationship between pNSCs and downstream progenitor cells. Using transgenic mouse models whereby dNSCs are labeled using a Cre-Lox system then subsequently ablated using the thymidine kinase system under the GFAP promoter, we have shown that pNSCs are non-GFAP expressing and can give rise to dNSCs in the forebrain. By taking advantage of the unique marker expression of Oct4 in pNSCs, we used Oct4CreERT2;ROSAyfpfl/fl;GFAPtk mice to selectively label pNSCs followed by complete depletion of dNSCs. As predicted, some dNSCs that returned over time expressed YFP, revealing a direct contribution from pre-labeled Oct4 expressing pNSCs. Together, these findings confirm the NSC lineage relationship in vivo, whereby the dNSC lies downstream of the pNSC in the adult forebrain.

ISBN: 9780355530858Subjects--Topical Terms:

588700
Neurosciences.

Neural Stem Cells in the Central Nervous System: Their Identification, Characterization and Lineage Relationship.
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520 $a Adult neural stem cells (NSC) reside in the periventricular region along the entire neuaxis. It is thought that a subset of mature astrocytes, expressing glial fibrillary acidic protein (GFAP), known as definitive NSCs (dNSC) are responsible for neurogenesis within the adult forebrain. We have identified a novel population of a rare, primitive NSC (pNSC) expressing low level of the pluripotency marker, Oct4. Both dNSC and pNSC can be isolated in vitro using neurosphere assays and differentiate into glial and neuronal cell types. Transplantation studies of pure pNSCs into the anterior rostral migratory stream of mice produced migrating neuroblasts and neurons in the olfactory bulb suggesting a potential lineage relationship between pNSCs and downstream progenitor cells. Using transgenic mouse models whereby dNSCs are labeled using a Cre-Lox system then subsequently ablated using the thymidine kinase system under the GFAP promoter, we have shown that pNSCs are non-GFAP expressing and can give rise to dNSCs in the forebrain. By taking advantage of the unique marker expression of Oct4 in pNSCs, we used Oct4CreERT2;ROSAyfpfl/fl;GFAPtk mice to selectively label pNSCs followed by complete depletion of dNSCs. As predicted, some dNSCs that returned over time expressed YFP, revealing a direct contribution from pre-labeled Oct4 expressing pNSCs. Together, these findings confirm the NSC lineage relationship in vivo, whereby the dNSC lies downstream of the pNSC in the adult forebrain.
520 $a In the non-neurogenic spinal cord niche, we have isolated pNSC and dNSC populations throughout development. We suggest a similar lineage relationship based on in vitro passaging experiments. Interestingly, the most abundant protein within mature myelin, myelin basic protein (MBP), inhibits proliferation which terminates NSC derived sphere formation in vitro . In a transgenic mouse model with conditional knock-out of MBP, the shiverer--/-- mouse, there is a significant enhancement of the number of NSCs isolated both naively and following injury compared to littermate or non-injured controls respectively.
520 $a In conclusion, we have identified two distinct NSC populations within the adult central nervous system that can be activated following injury but suppressed by MBP. Understanding the factors and conditions that impact these distinct populations of cells will shed light into developing novel stem cell-based regenerative medicine strategies.
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