Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 19 of 19 for “"transcriptional states"”.
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Decoding The Tumor and Immune Microenvironment In Pdac and Breast Cancer By Single Cell Sequencing.
… utilizes single cell RNA sequencing to identify transcriptional populations and gene changes for the purpose of immune-related cancer therapies. First we have characterized the T cell populations of the normal and malignant human pancreas. Furthermore, we utilized single cell TCR sequencing to …
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Co-optation of B Cell Developmental States in Malignancy and Autoimmunity
Transcriptional states provide a useful lens for understanding the diversity of cell identity and function. Cell state is regulated through both cell-intrinsic and -extrinsic mechanisms, and can diversify through tightly regulated transitions. However, perturbations to these regulatory mechanisms …
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Integrative multi-omics dissection of cancer cell states and susceptibility
… broad spectrum of unique genetic, epigenetic and transcriptional states, which are often concomitant with high degrees of plasticity in cell identity. These cell states and the fluidity therein are a major source of resistance to both chemotherapy and targeted therapy. Combinatorial efforts in …
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Biophysical approaches to single-cell characterization
… to describe complex tissues by characterizing transcriptional states of individual cells. Defining a cell’s position, both in regard to tissue margins and its social context, is essential for understanding the intrinsic and extrinsic variables that affect the transcriptional identity of …
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Functional genomic and transcriptomic tools for spatial and dynamic phenotypes
… have enabled high-throughput profiling of cell states, there is still a need for technologies that systematically probe and measure complex behaviors, including cell non-autonomous and dynamic phenotypes. In this thesis, we present the development of functional genomic and synthetic biology …
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Application of the single cell genomics in deciphering tumor heterogeneity and its role in tumor progression and drug resistance
… to lung adenocarcinoma. The diversity of transcriptional states spanned by tumor cells increased over time and was reproducible across tumors and mice, but was not explained by genomic copy number variation. Cancer cells progressively adopted alternate lineage identities, computationally …
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Mapping and modeling macrophages in tuberculosis
Immune cells polarize to diverse transcriptional and functional states to cause or resolve disease. Understanding this cellular diversity is critical to identifying new clinical interventions. Macrophages in tuberculosis granulomas are an archetype of these phenomena. Pinpointing the cellular …
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Transposable elements and the regulatory logic of hematopoietic differentiation
… that TEs in the human genome contribute to the transcriptional networks regulating lymphoid cells. De-repression of TEs in hematopoietic stem cells, enacted via modulation of TE chromatin silencing machinery, facilitates the development of natural killer (NK) cells during lymphoid …
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Collective Dynamics of Interacting Cell Types
… cell type transitions reflect their transcriptional proximity, suggesting organizing principles for cell lineage trees. Next, by coupling the transcriptional states of multistable single cells, I develop a general model of multicellular gene regulation that formalizes emerging notions …
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MULTI-OMIC LINEAGE TRACING PREDICTS THE MOLECULAR DRIVERS OF CANCER STEM CELLS IN TRIPLENEGATIVE BREAST CANCER EVOLUTION.
… treatment. Conversely, TICs exhibit two baseline transcriptional states and share a set of co-accessible chromatin regions, indicative of a pre-existing epigenetic basis for tumor initiation. Their behavior is orchestrated by specific gene regulatory networks driven by a set of transcription …
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Studies on the Histone Methyltransferase G9a
… An important means by which histones impact transcriptional activity is through site-specific enzymatic modification of the amino terminal histone "tails", which can alter the spectrum of chromatin-associated proteins and hence transcriptional states. Among the known modifications of …
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Mechanisms for Maintaining Cell Identity in C.elegans Olfactory Neurons
… that depends on developmentally determined transcriptional states and on environmental input. In neurons, which are both highly differentiated and highly sensitive to external stimuli, maintenance of identity is especially challenging. In this thesis, I describe the isolation and …
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Histone Modifications in Trypanosoma Brucei
… regulation of RNA elongation, and some kind of transcriptionally restrictive chromatin structure at inactive ES. In other organisms, the role of histone posttranslational modifications (PTMs) in influencing transcriptional states has been well-documented. To begin to understand the role of …
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Gene-regulatory circuitry of disease risk and progression
… gene regulation, its machinery, and complex transcriptional states. In this thesis, I build references of gene regulation and function in health and disease to interpret disease-linked genomic loci and develop methods to learn context-specific representations in order to understand how a …
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Identifying unique cell states in early liver oncogenesis with transcription coupled repair
… cells preferentially enter specific transcriptional states that interact with driver mutations to promote tumourigenesis. Characterising the aberrant transcriptional pathways of initiating cells could help elucidate the mechanisms for determining exactly which mutated cells will go on …
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Integrated, single-cell analysis of transcriptional phenotype and clonotypic identity
… receptor (BCR) variable region sequences to the transcriptional profiles of the same cells, but methods to perform analysis of the resulting data, which would enable the analysis of antigen-specific T and B cell phenotypes in their clonotypic context, remain limited. In this thesis, we develop …
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Tracing RNA biography: in situ transcriptome profiling by novel spatial omics technologies
… delineate the spatially resolved post-transcriptional regulations within transcriptomes, studying these events at the single-cell and single-molecule level. This advantage is important for mapping the complex network of transcriptional and post-transcriptional gene regulatory mechanisms …
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HIGH-THROUGHPUT PROFILING OF INNATE IMMUNE CELLS TO UNVEIL TUMOR ESCAPE MECHANISMS IN MATCHED COLORECTAL CANCER AND LIVER METASTASES
… In CRC, TAMs were enriched in inflammatory states that paradoxically supported immune activation while simultaneously laying the groundwork for metastatic dissemination. Conversely, CRLM was dominated by proliferative CTLA4high immunoregulatory TAMs, whose higher frequencies were associated …
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Cryo-EM Studies of Bacterial RNA Polymerase
… are difficult to obtain and the captured states may not always represent physiological states of the enzyme due to crystal packing artifacts. Recent advances in electron detectors and software enable near-atomic resolution structures of large biological complexes to be determined by single …