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Full-Text Articles in Life Sciences
The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista
The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista
Electronic Thesis and Dissertation Repository
The E26 transformation-specific transcription factors PU.1 and Spi-B are required for B cell maturation within the bone marrow. PU.1 expression is first detected in hematopoietic stem and progenitor cells, whereas Spi-B levels arise as early as the pro-B cell stage. The expression levels of both factors are maintained as B cells progress in development, and the lack of PU.1 and Spi-B at early stages impairs B cell development and can lead to B-cell leukemia. We hypothesized that PU.1 and Spi-B control events associated with the transition from high to low proliferative stages in B cell development and the absence of …
The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee
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 …
Counteracting Roles For The Related E26 Transformation Specific Transcription Factors Spi-B And Spi-C In Regulating Antibody-Forming Responses, Anne-Sophie Laramee
Counteracting Roles For The Related E26 Transformation Specific Transcription Factors Spi-B And Spi-C In Regulating Antibody-Forming Responses, Anne-Sophie Laramee
Electronic Thesis and Dissertation Repository
The activation of B cells culminates in a fate decision between plasma cell or memory B cell differentiation pathways. Mice lacking the Ets transcription factor Spi-B exhibit impaired secondary antibody (Ab)-forming responses. The role of the related factor Spi-C in Ab-forming responses remains unknown. Using Spib-/-Spic+/- mice, we showed that heterozygosity of Spi-C rescued reductions in secondary IgG1-secreting cell frequencies. Spib-/- and Spib-/-Spic+/- B cells generated increased frequencies of CD138+ cells, relative to WT B cells. Spib-/- B cells underwent accelerated differentiation compared to WT B cells, while Spib …
The E26 Transformation-Specific Transcription Factors Pu.1, Spi-B, And Spi-C Regulate Transcriptional Activation And Repression Of Nfkb1 To Control B Cell Development And Function, Stephen Ka Ho Li
Electronic Thesis and Dissertation Repository
PU.1, Spi-B, and Spi-C are highly related E26 transformation-specific family transcription factors that can bind nearly identical DNA sequences. PU.1 and Spi-B (encoded by Spi1 and Spib respectively) are important for B cell development and function, but the function of Spi-C (encoded by Spic) in B cells is not clear. The objective of this study was to determine PU.1, Spi-B, and Spi-C’s function during B cell development, and during TLR-mediated responses. It was hypothesized that PU.1 and Spi-B were required for positively regulating components of TLR responses, and Spi-C inhibited PU.1 and Spi-B targets. Spi1+/-Spib-/- ( …
Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto
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 …