Lineage restriction of the RARα gene expression in myeloid differentiation

Jun Zhu, Clare M. Heyworth, Annegret Glasow, Qiu Hua Huang, Kevin Petrie, Michel Lanotte, Gérard Benoit, Robert Gallagher, Samuel Waxman, Tariq Enver, Arthur Z Zelent

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 RARα (primarily the RARα1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARα expression (particularly the RARα2 isoform) was seen. In contrast, expression of both RARα isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRα expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARγ2 and RXRβ remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARα 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 RARα 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 RARα2 RARa2 expression, can exert inhibitory effects on erythroid differentiation.

Original languageEnglish (US)
Pages (from-to)2563-2567
Number of pages5
JournalBlood
Volume98
Issue number8
DOIs
StatePublished - Oct 15 2001
Externally publishedYes

Fingerprint

Retinoic Acid Receptors
Gene expression
Retinoid X Receptors
Gene Expression
Protein Isoforms
Retinoids
Tretinoin
Cells
Myelopoiesis
Erythropoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Granulocytes
Intercellular Signaling Peptides and Proteins
Stem Cells
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

Zhu, J., Heyworth, C. M., Glasow, A., Huang, Q. H., Petrie, K., Lanotte, M., ... Zelent, A. Z. (2001). Lineage restriction of the RARα gene expression in myeloid differentiation. Blood, 98(8), 2563-2567. https://doi.org/10.1182/blood.V98.8.2563

Lineage restriction of the RARα gene expression in myeloid differentiation. / Zhu, Jun; Heyworth, Clare M.; Glasow, Annegret; Huang, Qiu Hua; Petrie, Kevin; Lanotte, Michel; Benoit, Gérard; Gallagher, Robert; Waxman, Samuel; Enver, Tariq; Zelent, Arthur Z.

In: Blood, Vol. 98, No. 8, 15.10.2001, p. 2563-2567.

Research output: Contribution to journalArticle

Zhu, J, Heyworth, CM, Glasow, A, Huang, QH, Petrie, K, Lanotte, M, Benoit, G, Gallagher, R, Waxman, S, Enver, T & Zelent, AZ 2001, 'Lineage restriction of the RARα gene expression in myeloid differentiation', Blood, vol. 98, no. 8, pp. 2563-2567. https://doi.org/10.1182/blood.V98.8.2563
Zhu J, Heyworth CM, Glasow A, Huang QH, Petrie K, Lanotte M et al. Lineage restriction of the RARα gene expression in myeloid differentiation. Blood. 2001 Oct 15;98(8):2563-2567. https://doi.org/10.1182/blood.V98.8.2563
Zhu, Jun ; Heyworth, Clare M. ; Glasow, Annegret ; Huang, Qiu Hua ; Petrie, Kevin ; Lanotte, Michel ; Benoit, Gérard ; Gallagher, Robert ; Waxman, Samuel ; Enver, Tariq ; Zelent, Arthur Z. / Lineage restriction of the RARα gene expression in myeloid differentiation. In: Blood. 2001 ; Vol. 98, No. 8. pp. 2563-2567.
@article{9a6154a863b64800845fb1c54ff83249,
title = "Lineage restriction of the RARα gene expression in myeloid differentiation",
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 RARα (primarily the RARα1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARα expression (particularly the RARα2 isoform) was seen. In contrast, expression of both RARα isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRα expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARγ2 and RXRβ remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARα 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 RARα 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 RARα2 RARa2 expression, can exert inhibitory effects on erythroid differentiation.",
author = "Jun Zhu and Heyworth, {Clare M.} and Annegret Glasow and Huang, {Qiu Hua} and Kevin Petrie and Michel Lanotte and G{\'e}rard Benoit and Robert Gallagher and Samuel Waxman and Tariq Enver and Zelent, {Arthur Z}",
year = "2001",
month = "10",
day = "15",
doi = "10.1182/blood.V98.8.2563",
language = "English (US)",
volume = "98",
pages = "2563--2567",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Lineage restriction of the RARα gene expression in myeloid differentiation

AU - Zhu, Jun

AU - Heyworth, Clare M.

AU - Glasow, Annegret

AU - Huang, Qiu Hua

AU - Petrie, Kevin

AU - Lanotte, Michel

AU - Benoit, Gérard

AU - Gallagher, Robert

AU - Waxman, Samuel

AU - Enver, Tariq

AU - Zelent, Arthur Z

PY - 2001/10/15

Y1 - 2001/10/15

N2 - 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 RARα (primarily the RARα1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARα expression (particularly the RARα2 isoform) was seen. In contrast, expression of both RARα isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRα expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARγ2 and RXRβ remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARα 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 RARα 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 RARα2 RARa2 expression, can exert inhibitory effects on erythroid differentiation.

AB - 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 RARα (primarily the RARα1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARα expression (particularly the RARα2 isoform) was seen. In contrast, expression of both RARα isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRα expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARγ2 and RXRβ remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARα 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 RARα 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 RARα2 RARa2 expression, can exert inhibitory effects on erythroid differentiation.

UR - http://www.scopus.com/inward/record.url?scp=0035886025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035886025&partnerID=8YFLogxK

U2 - 10.1182/blood.V98.8.2563

DO - 10.1182/blood.V98.8.2563

M3 - Article

C2 - 11588055

AN - SCOPUS:0035886025

VL - 98

SP - 2563

EP - 2567

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -