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The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee Aug 2018

The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee

Electronic Thesis and Dissertation Repository

PU.1 is a transcription factor essential for myeloid development. High PU.1 levels promote cell cycle arrest and differentiation. Low levels promote proliferation and have been associated with leukemia. BN mice are homozygous for a hypomorphic allele of Spi1 that results in expression of PU.1 at 20% of normal levels. Induction of PU.1 expression in BN myeloid progenitor cells causes cell cycle arrest, differentiation, and the upregulation of microRNAs targeting lipid metabolic genes. Acly encoding ATP citrate lyase (ACL) was one of these targets. ACL produces acetyl-CoA which is essential for fatty acid synthesis. We hypothesized that inhibiting ACL would cause …


Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto Aug 2013

Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto

Electronic Thesis and Dissertation Repository

Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. PU.1 is a transcription factor that is required for the development of nearly all white blood cell types of the immune system, including B cells, granulocytes, and monocytes. Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. We hypothesized that reduced expression of PU.1 in Sfpi1BN/BNmyeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle. Results indicate that NOD/SCID/γc …