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Lineage restriction of the RARalpha gene expression in myeloid differentiation.

Zhu, J, Heyworth, C M, Glasow, A, Huang, Q H, Petrie, Kevin, Lanotte, M, Benoit, G, Gallagher, R, Waxman, S, Enver, T and Zelent, A (2001) Lineage restriction of the RARalpha gene expression in myeloid differentiation. Blood, 98 (8). pp. 2563-7. ISSN 0006-4971

Item Type: Article

Abstract

To better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, expression of both RARalpha isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRalpha expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARalpha activities, respectively, which at physiological all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12420
Identification Number: https://doi.org/10.1182/blood.V98.8.2563
ISSN: 0006-4971
URI: http://sure.sunderland.ac.uk/id/eprint/12420
Official URL: https://ashpublications.org/blood/article/98/8/256...

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 09:53
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: J Zhu
Author: C M Heyworth
Author: A Glasow
Author: Q H Huang
Author: M Lanotte
Author: G Benoit
Author: R Gallagher
Author: S Waxman
Author: T Enver
Author: A Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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