<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-7.xsd"><mods:titleInfo><mods:title>The role of LINE-1 retrotransposition in the accumulating DNA damage of neural stem cells</mods:title></mods:titleInfo><mods:typeOfResource>text</mods:typeOfResource><mods:name type="personal"><mods:namePart>Huang, Constance</mods:namePart><mods:role><mods:roleTerm type="text">creator</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Kreiling, Jill</mods:namePart><mods:role><mods:roleTerm type="text">Advisor</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Reenan, Robert</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Liu, Judy</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="corporate"><mods:namePart>Brown University. Department of Molecular Pharmacology, Physiology and Biotechnology</mods:namePart><mods:role><mods:roleTerm type="text">sponsor</mods:roleTerm></mods:role></mods:name><mods:originInfo><mods:copyrightDate>2019</mods:copyrightDate></mods:originInfo><mods:physicalDescription><mods:extent>5, 23 p.</mods:extent><mods:digitalOrigin>born digital</mods:digitalOrigin></mods:physicalDescription><mods:note type="thesis">Thesis (Sc. M.)--Brown University, 2019</mods:note><mods:genre authority="aat">theses</mods:genre><mods:abstract>Neural stem cells (NSCs) are multipotent cells that have the potential to differentiate into multiple lineages that ultimately populate the brain with a mosaic of cells of various function. However, in the later stages of life, the loss of proliferative capability of NSCs can lead to the onset of many neurodegenerative diseases. One of the possible mechanisms behind this loss of function could be the expression of LINE-1 (L1) retrotransposable elements in the brain. These self-autonomous elements have the capability of randomly inserting into the host genome and are found to be highly expressed in the brain as well as throughout various tissues in the body. There is mounting evidence to show age-related changes to chromatin structure results in the increased rates of unsuccessful retrotransposable events that can ultimately lead to accumulating DNA damage. With the presence of L1 found to be in the brain, it is possible that the brain is susceptible to increasing DNA damage that has been demonstrated to induce senescence in neural stem cells.&#13;
To provide insight into this possible mechanism of action, NSCs were transfected L1 elements under tetracycline inducible promoters. Once activated, the NSCs were screened for DNA damage and senescence associated phenotype (SASP) markers to determine its impact on the functionality of NSCs. This project aims to implicate the role of L1 expression in the accumulation of DNA damage that ultimately results in the senescence and loss of function in neural stem cells.</mods:abstract><mods:subject><mods:topic>Adult Neurogenesis</mods:topic></mods:subject><mods:subject><mods:topic>retrotransposon</mods:topic></mods:subject><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/00837570"><mods:topic>Brain</mods:topic></mods:subject><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01036275"><mods:topic>Neural stem cells</mods:topic></mods:subject><mods:language><mods:languageTerm authority="iso639-2b">English</mods:languageTerm></mods:language><mods:recordInfo><mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource><mods:recordCreationDate encoding="iso8601">20190603</mods:recordCreationDate></mods:recordInfo><mods:identifier type="doi">10.26300/zzp8-kf77</mods:identifier><mods:accessCondition type="rights statement" xlink:href="http://rightsstatements.org/vocab/InC/1.0/">In Copyright</mods:accessCondition><mods:accessCondition type="restriction on access">Collection is open for research.</mods:accessCondition></mods:mods>