The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis

The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis

Bibliographic Details
Main Author: Houston, Isaac Benjamin
Language:English
Published: University of Cincinnati / OhioLINK 2007
Subjects:
PU.1
Hematopoiesis
Lineage Fate
Leukemia
Acute Myeloid Leukemia
Myelopoiesis
Erythropoiesis
Transcription Factor
Hypomorphic
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1184351116
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11843511162021-08-03T06:12:08Z The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis Houston, Isaac Benjamin PU.1 Hematopoiesis Lineage Fate Leukemia Acute Myeloid Leukemia Myelopoiesis Erythropoiesis Transcription Factor Hypomorphic The Ets family transcription factor PU.1 (encoded by <i>Sfpi1</i>) is essential for both myeloid and lymphoid development. Previous data has demonstrated that high concentrations of PU.1 protein promote macrophage development <i>in vitro</i>, whereas low concentrations permit B cell development <i>in vitro</i>. Additionally, enforced expression of PU.1 assists in erythroblast immortalization and murine erythroleukemia. These data demonstrate that alteration of PU.1 expression levels directly affects hematopoietic development. We hypothesized that high level expression of PU.1 in developing progenitors correlates with myeloid lineage commitment. We tested this hypothesis by several methods. First, we immortalized murine fetal liver hematopoietic progenitors by retroviral expression of PU.1 in combination with granulocyte-monocyte colony stimulating factor stimulation. Immortalized cells possessed characteristics of multiple lineages and were demonstrated to be bipotential upon removal of exogenous PU.1. Second, we utilized an allele of <i>Sfpi1</i> (termed BN), and an allele in which neomycin was removed (<i>Sfpi1<sup>Blac</sup></i>), which results in hypomorphic expression of PU.1. <i>Sfpi1<sup>BN/BN</sup></i> mice showed an intrinsic block to early B cell development. In addition, myeloid development was impaired in <i>Sfpi1<sup>BN/BN</sup></i> fetal liver whereas neonatal <i>Sfpi1<sup>BN/BN</sup></i> mice have a dramatic expansion of immature myeloid cells. These results demonstrate that over-expression of PU.1 can block differentiation prior to myeloid or erythroid commitment. Additionally, high levels of PU.1 are required for B cell specification, but not myeloid. These results demonstrate the critical importance of an appropriate threshold of PU.1 activity for normal hematopoiesis. 2007-10-08 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1184351116 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1184351116 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic PU.1
Hematopoiesis
Lineage Fate
Leukemia
Acute Myeloid Leukemia
Myelopoiesis
Erythropoiesis
Transcription Factor
Hypomorphic
spellingShingle PU.1
Hematopoiesis
Lineage Fate
Leukemia
Acute Myeloid Leukemia
Myelopoiesis
Erythropoiesis
Transcription Factor
Hypomorphic
Houston, Isaac Benjamin
The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
author Houston, Isaac Benjamin
author_facet Houston, Isaac Benjamin
author_sort Houston, Isaac Benjamin
title The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
title_short The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
title_full The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
title_fullStr The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
title_full_unstemmed The Importance of Maintaining PU.1 Expression Levels During Hematopoiesis
title_sort importance of maintaining pu.1 expression levels during hematopoiesis
publisher University of Cincinnati / OhioLINK
publishDate 2007
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1184351116
work_keys_str_mv AT houstonisaacbenjamin theimportanceofmaintainingpu1expressionlevelsduringhematopoiesis
AT houstonisaacbenjamin importanceofmaintainingpu1expressionlevelsduringhematopoiesis
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