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Titolo:
Multipotent hematopoietic cell lines derived from C/EBP alpha(-/-) knockout mice display granulocyte macrophage-colony-stimulating factor, granulocyte-colony-stimulating factor, and retinoic acid-induced granulocytic differentiation
Autore:
Collins, SJ; Ulmer, J; Purton, LE; Darlington, G;
Indirizzi:
Fred Hutchinson Canc Res Ctr, Human Biol div, Seattle, WA 98109 USA Fred Hutchinson Canc Res Ctr Seattle WA USA 98109 , Seattle, WA 98109 USA Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Pathol, Houston, TX 77030 USA Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 ton Ctr Aging, Houston, TX 77030 USA
Titolo Testata:
BLOOD
fascicolo: 8, volume: 98, anno: 2001,
pagine: 2382 - 2388
SICI:
0006-4971(20011015)98:8<2382:MHCLDF>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING PROTEIN-ALPHA; C/EBP-ALPHA; DEFICIENT MICE; NEUTROPHIL DIFFERENTIATION; GENE-EXPRESSION; RECEPTOR-ALPHA; MYELOID CELLS; GRANULOPOIESIS; PROGENITORS; PROMOTER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Collins, SJ Fred Hutchinson Canc Res Ctr, Human Biol div, 1100 Fairview Ave N, Seattle, WA 98109 USA Fred Hutchinson Canc Res Ctr 1100 Fairview Ave NSeattle WA USA 98109
Citazione:
S.J. Collins et al., "Multipotent hematopoietic cell lines derived from C/EBP alpha(-/-) knockout mice display granulocyte macrophage-colony-stimulating factor, granulocyte-colony-stimulating factor, and retinoic acid-induced granulocytic differentiation", BLOOD, 98(8), 2001, pp. 2382-2388

Abstract

The transcription factor C/EBP alpha is an important mediator of granulocyte differentiation and regulates the expression of multiple granulocyte-specific genes including the granulocyte-colony-stimulating factor (GCSE) receptor, neutrophil elastase, and myeloperoxidase. Indeed C/EBP alpha knockoutmice display a profound block in granulocyte differentiation. To study this block in granulocytic differentiation in more detail, retroviral vector-mediated transduction of a dominant-negative retinoic acid receptor was usedto establish hematopoietic growth factor-dependent, lympho-myeloid progenitor cell lines from the fetal livers of both the C/EBP alpha knockout animals (C/EBP alpha(-/-)) and their heterozygous littermates (C/EBP alpha(+/-)). Surprisingly, the C/EBP alpha(-/-) cell lines displayed significant spontaneous granulocytic differentiation, and this differentiation was markedly enhanced when the cells were stimulated with granulocyte macrophage (GM)-CSF. This GM-CSF-mediated differentiation was associated with the up-regulation of G-CSF receptor mRNA, and the combination of GM-CSF and G-CSF generated more than 95% mature neutrophils in the C/EBP alpha(-/-) cultures. The addition of all-trans retinoic acid also enhanced this granulocytic differentiation of the cultured C/EBP alpha(-/-) cells, indicating that the activated retinoic acid receptors can enhance granulocytic differentiation through a molecular pathway that is independent of C/EBP alpha. These studies clearly indicate that terminal granulocytic differentiation associated with the up-regulation of C/EBP alpha -responsive genes can occur in the absence of C/EBP alpha, and they indicate the existence of multiple independent molecular pathways potentially used by primitive hematopoietic precursors that can lead to the development of mature granulocytes. (C) 2001 by The American Society of Hematology.

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Documento generato il 09/04/20 alle ore 06:34:57