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

TY - JOUR

T1 - Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation.

AU - McIvor, Zoe

AU - Hein, Sybill

AU - Fiegler, Heike

AU - Schroeder, Timm

AU - Stocking, Carol

AU - Just, Ursula

AU - Cross, Michael

PY - 2003

Y1 - 2003

N2 - OBJECTIVES: 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 bipotent granulocyte/macrophage progenitors. In contrast, continuous expression of PU.1 resulted in a strong bias toward macrophage rather than granulocyte differentiation. CONCLUSIONS: These results demonstrate promyeloid effects of PU.1 at two distinct stages of hematopoiesis.

AB - OBJECTIVES: 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 bipotent granulocyte/macrophage progenitors. In contrast, continuous expression of PU.1 resulted in a strong bias toward macrophage rather than granulocyte differentiation. CONCLUSIONS: These results demonstrate promyeloid effects of PU.1 at two distinct stages of hematopoiesis.

M3 - SCORING: Zeitschriftenaufsatz

VL - 31

SP - 39

EP - 47

JO - EXP HEMATOL

JF - EXP HEMATOL

SN - 0301-472X

IS - 1

M1 - 1

ER -