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Direct Reprogramming of NG2 Glia int...

Baral, Ashmita,

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Direct Reprogramming of NG2 Glia into Neurons /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Direct Reprogramming of NG2 Glia into Neurons // Ashmita Baral.
作者:	Baral, Ashmita,
面頁冊數:	1 electronic resource (151 pages)
附註:	Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
Contained By:	Dissertations Abstracts International87-05B.
標題:	Neurosciences. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=32279910
ISBN:	9798297989221

Direct Reprogramming of NG2 Glia into Neurons /
Baral, Ashmita,

Direct Reprogramming of NG2 Glia into Neurons /Ashmita Baral. - 1 electronic resource (151 pages)

Source: Dissertations Abstracts International, Volume: 87-05, Section: B.

Conditions such as traumatic brain injury, stroke and other neurodegenerative diseases all have neuronal loss resulting in permanent damage. Our lab's approach for therapeutic neuronal replacement is through the direct reprogramming of dividing glial cells into neurons. Oligodendrocyte progenitor cells (OPCs or NG2 glia) are an abundant and widespread glial progenitor cell type that continue to proliferate throughout life, thus making them an ideal candidate for neuronal reprogramming. Previously, our lab and others have published successful direct reprogramming of rat OPCs into neurons. However, there is a current lack of knowledge on the capacity of resident human primary OPCs to be reprogrammed into various neuronal subtypes necessary for brain repair. Additionally, we addressed a gap in commonly used approaches to cellular reprogramming using forced single or multiple instructive genes which does not allow control of the orchestrated sequence of instructive signals seen in normal development. The goal of this thesis is to first characterize the naive state and reprogramming capacity of primary human derived OPCs and compare with existing rat paradigms. We found that fetal human OPCs have a more heterogenous starting population relative to rat OPCs. Upon retroviral reprogramming using the pioneering transcription factor Ngn2, we compared reprogramming of human and rat OPCs using immunostaining. Secondly, we have developed a biologically and clinically relevant tool for improved reprogramming. To do this we engineered a regulatable gene expression system to control temporal expression of sequential genes. This novel switch expression system for reprogramming is an innovative approach that we hypothesize can more closely mimic in vivo lineage specification by permitting control of the timing of lineage specification. Utilizing a regulatable retroviral vector toolbox will aid in a biologically relevant study of the capacity of the OPCs to reprogram into neurons. Together, these studies define baseline features of human and rat OPCs relevant to fate conversion and provide a versatile toolkit to improve efficiency and fidelity of generating neurons from OPCs for future brain-repair applications.

English

ISBN: 9798297989221Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Induced reprogramming

Direct Reprogramming of NG2 Glia into Neurons /
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520 $a Conditions such as traumatic brain injury, stroke and other neurodegenerative diseases all have neuronal loss resulting in permanent damage. Our lab's approach for therapeutic neuronal replacement is through the direct reprogramming of dividing glial cells into neurons. Oligodendrocyte progenitor cells (OPCs or NG2 glia) are an abundant and widespread glial progenitor cell type that continue to proliferate throughout life, thus making them an ideal candidate for neuronal reprogramming. Previously, our lab and others have published successful direct reprogramming of rat OPCs into neurons. However, there is a current lack of knowledge on the capacity of resident human primary OPCs to be reprogrammed into various neuronal subtypes necessary for brain repair. Additionally, we addressed a gap in commonly used approaches to cellular reprogramming using forced single or multiple instructive genes which does not allow control of the orchestrated sequence of instructive signals seen in normal development. The goal of this thesis is to first characterize the naive state and reprogramming capacity of primary human derived OPCs and compare with existing rat paradigms. We found that fetal human OPCs have a more heterogenous starting population relative to rat OPCs. Upon retroviral reprogramming using the pioneering transcription factor Ngn2, we compared reprogramming of human and rat OPCs using immunostaining. Secondly, we have developed a biologically and clinically relevant tool for improved reprogramming. To do this we engineered a regulatable gene expression system to control temporal expression of sequential genes. This novel switch expression system for reprogramming is an innovative approach that we hypothesize can more closely mimic in vivo lineage specification by permitting control of the timing of lineage specification. Utilizing a regulatable retroviral vector toolbox will aid in a biologically relevant study of the capacity of the OPCs to reprogram into neurons. Together, these studies define baseline features of human and rat OPCs relevant to fate conversion and provide a versatile toolkit to improve efficiency and fidelity of generating neurons from OPCs for future brain-repair applications.
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