Date of Completion
Spring 5-17-2021
Project Advisor(s)
Joseph LoTurco, Joanne Conover, Charles Giardina
University Scholar Major
Molecular and Cell Biology
Disciplines
Bioinformatics | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Computational Biology | Genetics | Immunotherapy | Molecular and Cellular Neuroscience | Molecular Genetics | Neoplasms
Abstract
Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to derive a transcriptomic profile of the heterogeneous cell types composing ST-EPN mouse tumors. Among the 20,000 cells sequenced, approximately two-thirds of the cells did not express the oncogene. These cells represent various types of immune cells, such as B-lymphocytes, T-cells, and macrophages; stromal cells, and different neural cell types (i.e. oligodendrocytes). Although ZFTA-RELA has been shown to activate NF-κB effector genes, there was not a ubiquitous upregulation of such genes across the cells enriched for ZFTA-RELA expression. Subclustering these tumorigenic cells revealed distinct subpopulations characterized by upregulation of non-NFκB pathways involved in cell proliferation, extracellular environment reorganization, and immune activation. We identified a list of specific markers for these cellular conditions to better characterize the processes underlying ST-EPN aggressiveness and immunological responses.
Recommended Citation
He, James, "Identifying the Cell Composition and Clonal Diversity of Supratentorial Ependymoma Using Single Cell RNA-Sequencing" (2021). University Scholar Projects. 67.
https://digitalcommons.lib.uconn.edu/usp_projects/67
Included in
Bioinformatics Commons, Cancer Biology Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Computational Biology Commons, Genetics Commons, Immunotherapy Commons, Molecular and Cellular Neuroscience Commons, Molecular Genetics Commons, Neoplasms Commons
