Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Collaborative Specialization

Developmental Biology

Supervisor

DeKoter, Rodney P.

Abstract

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 cell cycle arrest. BN cells treated with an ACL inhibitor were cell cycle arrested. Acetyl-CoA supplementation rescued cell cycle. The results suggest fatty acid metabolism plays a crucial role in cell cycle progression. Elucidating the mechanism of PU.1’s role in lipid metabolism and cell cycle regulation has implications for disease.

Available for download on Thursday, July 09, 2020

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