000008696 001__ 8696
000008696 005__ 20231129124944.0
000008696 0247_ $$2DOI$$a10.6083/fb4948977
000008696 037__ $$aETD
000008696 245__ $$aSingle-cell approaches for deciphering complex tissue heterogeneity
000008696 260__ $$bOregon Health and Science University
000008696 269__ $$a2020
000008696 336__ $$aDissertation
000008696 502__ $$bPh.D.
000008696 520__ $$aDuring healthy development and aging, somatic mutations aggregate in tissues, lending different mutational profiles to cells within these tissues. Similarly, developmental processes create the functional diversity necessary for normal tissue function. Cancer arises from the aberrant functioning of these processes. Mutational profiles and epigenetic regulation support uncontrolled growth of neoplasms with the potential ability to invade nearby tissues. The resulting intra-tumor heterogeneity contributes to evasion of drug pressures via Darwinian selection, and cell-state plasticity allows for dynamic shifts in regulation into drug-resistant persistor states. While bulk genomic assays profile averages of sampled cell populations, single-cell approaches allow for a picture of the heterogeneity of healthy and diseased complex tissues. In this dissertation, I assess the state of the single-cell field with a focus on assays characterizing whole genome copy number variation and chromatin accessibility. I show three examples of profiling heterogeneity by (i) assessing the genomes of thousands of cells in healthy and diseased tissues (ii) mapping the chromatin landscape of the murine hippocampus, and (iii) characterizing the development of Trametinib resistance through cell state plasticity across basal-like triple negative breast cancer cell lines.
000008696 542__ $$fIn copyright - single owner
000008696 650__ $$aDNA Copy Number Variations$$038765
000008696 650__ $$aHippocampus$$020217
000008696 650__ $$aEpigenomics$$039014
000008696 650__ $$aBreast Neoplasms$$015809
000008696 6531_ $$atrametinib
000008696 691__ $$aSchool of Medicine$$041369
000008696 692__ $$aDepartment of Molecular and Medical Genetics$$041428
000008696 7001_ $$aTörkenczy, Kristóf A.
000008696 8564_ $$94d43d9c6-4497-4bea-84ef-ec3d6ada1158$$s6274811$$uhttps://digitalcollections.ohsu.edu/record/8696/files/Torkenczy.Kristof.2020.pdf
000008696 905__ $$a/rest/prod/fb/49/48/97/fb4948977
000008696 909CO $$ooai:digitalcollections.ohsu.edu:8696$$pstudent-work
000008696 980__ $$aTheses and Dissertations