PuSH - Publication Server of Helmholtz Zentrum München: Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation.

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McIvor, Z.* ; Hein, S.* ; Fiegler, H. ; Schroeder, T. ; Stocking, C.* ; Just, U. ; Cross, M.*

Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation.

Exp. Hematol. 31, 39-47 (2003)

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Objective. The Ets-family transcription factor PU.1 is expressed specifically in the hematopoietic system, in which it is absolutely required for the generation of B lymphocytes and macrophages. In contrast. overexpression of PU.1 blocks terminal differentiation of the erythroid lineage, in which it can act as an oncogene. In this study we used a multipotential progenitor cell line to examine the effects of PU.1 overexpression on myeloerythroid commitment within a single model system. Materials and Methods. PU.1 cDNA was introduced transiently and stably into the multipotent, nonleukemic hemopoietic cell line FDCPmix. Transiently transfected cells were isolated by fluorescence-activated cell sorting within 18 hours of transfection. Stable transfectants were selected by antibiotic resistance over a number of weeks. The effects of short- and long-term overexpression of PU.1 on self-renewal, proliferation, and differentiation were investigated. Results. A transient pulse of expression in multipotent progenitor cells eliminated the options of self-renewal and erythroid differentiation, resulting in commitment to the myeloid lineage. However, this transient pulse of expression did not affect the subsequent lineage choice of bi-potent granulocyte/macrophage progenitors. In contrast, continuous expression of PU.1 resulted in a strong bias toward macrophage rather than granulocyte differentiation. Conclusion. These results demonstrate promyeloid effects of PU.1 at two distinct stages of hematopoiesis.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords TRANSCRIPTION FACTOR PU.1; STIMULATING FACTOR-RECEPTOR; MURINE ERYTHROLEUKEMIA-CELLS; HEMATOPOIETIC PROGENITORS; DNA-BINDING; STEM-CELLS; MYB-ETS; GENE; OVEREXPRESSION; PROLIFERATION

ISSN (print) / ISBN 0301-472X

e-ISSN 0301-472X

Journal Experimental Hematology

Quellenangaben Volume: 31, Issue: 1, Pages: 39-47

Publisher Elsevier

Non-patent literature Publications

Reviewing status Peer reviewed