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Deciphering the Hematopoietic Gene Regulatory Architecture


The immune system is a complex and interactive network of diverse cell types, with a myriad of functional properties that are fundamental to maintaining an immunological-responsive balance within an organism. Thus, coordinated organization of cellular differentiation is established early and throughout the development of an organism, resulting in the generation of the interacting innate and adaptive immune systems. The temporal component is critical for capturing transient regulatory events during cellular differentiation. Thus, high-resolution analyses are necessary to derive immune regulatory dynamics. To address this, I focused my graduate studies on the genome-wide analysis of cellular differentiation with a primary focus on: (i) myeloid transcriptional and cis-regulatory modules; (ii) dynamic myeloid gene regulatory networks; and (iii) analysis of the expression and accessible chromatin landscape in single-cells. Utilizing high-resolution time-series analyses, I have identified temporal modules of cell-type specific cis-regulatory and transcriptional regulation during myeloid and pre-B cell differentiation. Such genome-wide modules were then utilized to infer novel regulatory interactions and generation of dynamic gene regulatory networks during myeloid differentiation. Secondly, both an independent and integrative analysis of single-cell chromatin maps and expression patterns of pre-B cell differentiation, revealing complex relationships between the chromatin landscape and TF regulators in differentiating single-cells. Take together; these results depict the temporal dynamics mediated across the cis-regulatory landscape and transcriptional regulators that ultimately shape differentiating mammalian cells across the innate and adaptive immune systems.

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