Single-cell transcriptional profiling of Huntington's disease in human and mouse models
Author(s)
Pineda, Sergio Sebastian.![Thumbnail](/bitstream/handle/1721.1/129176/1227278096-MIT.pdf.jpg?sequence=4&isAllowed=y)
Download1227278096-MIT.pdf (13.50Mb)
Alternative title
Single-cell transcriptional profiling of HD in human and mouse models
Other Contributors
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science.
Advisor
Manolis Kellis and Myriam Heiman.
Terms of use
Metadata
Show full item recordAbstract
Uncovering the mechanisms that drive cell type-specific vulnerability differences in Huntington's disease (HD) is an imperative prerequisite to finding a reliable therapeutic target. The most affected regions and cell types likely possess vulnerability factors or lack protective factors possessed by other cell types that lead to their early dysfunction and enhanced loss, but such factors remain elusive. In order to characterize the cell type-specific responses induced by mutant huntingtin (mHTT), we applied single-nucleus RNA sequencing to pro- file gene expression changes in human HD and two commonly used mouse models of HD. In the process, we produced the first molecular atlas of the human neostriatum, identified new and previously unobserved cell types, and examined the molecular conservation of this brain region across species. We also developed and documented new computational methods and techniques for curating and analyzing single-cell data from post-mortem human brain samples.
Description
Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, September, 2020 Cataloged from student-submitted PDF version of thesis. Includes bibliographical references (pages 45-48).
Date issued
2020Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer SciencePublisher
Massachusetts Institute of Technology
Keywords
Electrical Engineering and Computer Science.