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Richard Dahl

Publications and source records attributed to Richard Dahl.

10 recordsLinked to original sources
PubMed2003

Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPalpha ratio and granulocyte colony-stimulating factor.

Hematopoietic transcription factors are essential for specifying cell fates; however, the function of cytokines in such developmental decisions is unresolved. We demonstrate here that haploinsufficiency for the gene encoding the transcription factor PU.1 partially suppresses the neutropenia of mice deficient in granulocyte colony-stimulating factor. This suppression was due to an increase in granulocytic progenitors and a diminution of monocytic progenitors. With (PU.1+/-) ES cells as well as (PU.1-/-) hematopoietic progenitors, we show that higher expression of PU.1 is needed for macrophage than for neutrophil development. In a (PU.1-/-) progenitor cell line, in which graded activity of PU.1 regulates neutrophil versus macrophage development, granulocyte colony-stimulating factor signaling supported the neutrophil cell fate by increasing expression of the neutrophil transcription factor C/EBPalpha in relation to expression of PU.1. Collectively, these results indicate that cytokines can promote cell fate decisions by altering the relative concentrations of lineage-determining transcriptional regulators.

Animals↗
PubMed2002

Spi-B can functionally replace PU.1 in myeloid but not lymphoid development.

Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1(-/-) mice. In contrast, mice lacking the highly related protein Spi-B generate all hematopoietic lineages but display a B-cell receptor signaling defect. These distinct phenotypes could result from functional differences between PU.1 and Spi-B or their unique temporal and tissue-specific expression (PU.1: myeloid and B cells; Spi-B: B cells only). To address this question, we introduced the Spi-B cDNA into the murine PU.1 locus by homologous recombination. In the absence of PU.1, Spi-B rescued macrophage and granulocyte development when assayed by in vitro differentiation of embryonic stem cells. Adherent, CD11b(+)/F4/80(+) cells capable of phagocytosis were detected in PU.1(Spi-B/Spi-B) embryoid bodies, and myeloid colonies were present in hematopoietic progenitor assays. Despite its ability to rescue myeloid differentiation, Spi-B did not rescue lymphoid development in a RAG-2(-/-) complementation assay. These results demonstrate an important difference between PU.1 and Spi-B. Careful comparison of these Ets factors will delineate important functional domains of PU.1 involved in lymphocyte lineage commitment and/or maturation.

Animals↗
PubMed2002

Who pays for e-Junk?

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Conservation of Natural Resources↗
PubMed2002

A BETR way to track toxic pollutants.

Why are chemicals that have been banned for over a decade still being detected in the environment? How is it that chemicals and other pollutants such as particulate matter turn up hundreds or even thousands of miles from their sources? These are just two of the questions that a team of American and Canadian scientists hope will be answered using a model they have developed to track pollutants across North America. In the short term, the model's developers are concentrating on using it to assess rates of exposure from food sources, but they hope to expand the model to include global data, a step they hope will help policy makers better understand the consequences of pollution.

Air Movements↗
PubMedDate not supplied

The importance of PU.1 concentration in hematopoietic lineage commitment and maturation.

PU.1 is an Ets family transcription factor that is required for the development of myeloid and lymphoid cells. Since PU.1 is required for several different lineages it has been unclear what role PU.1 has in deciding whether a hematopoietic progenitor cell differentiates into a macrophage, granulocyte, or B cell. Recent studies have demonstrated that different cellular concentrations of PU.1 may direct distinct cell fates, with the highest concentrations of PU.1 required for macrophage development and lower concentrations for granulocytic and B-cell fate adoption. Since PU.1 transactivation activity is inhibited by the granulocytic factor, C/EBPalpha and the B-cell factor BSAP, high concentrations of PU.1 may be required for macrophage development in order to overcome the negative effects of alternative lineage specific factors. Lastly, PU.1 upregulation is implicated in the maturation of myeloid cells once they have committed to the macrophage and granulocytic lineages. PU.1 activity is inhibited in some cases of acute myelogenous leukemia (AML), therefore, inhibition of PU.1 induced maturation may be a critical step in leukemogenesis.

Cell Differentiation↗