Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis

C. Labbaye, M. Valtieri, T. Barberi, E. Meccia, B. Masella, E. Pelosi, G. L. Condorelli, U. Testa, C. Peschle

Research output: Contribution to journalArticle

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Abstract

We have explored the expression of the transcription factors GATA-1, GATA- 2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus. GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced as early as 3 h after growth factor stimulus, but then declines in advanced erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs and proteins, though not detected in quiescent HPCs, are gradually induced at 24-48 h in both erythroid and granulocytic culture. Beginning at late differentiation/early maturation stage, both transcription factors are further accumulated in the erythroid pathway, whereas they are suppressed in the granulopoietic series. Similarly, the erythropoietin receptor (EpR) is induced and sustainedly expressed during erythroid differentiation, although beginning at later times (i.e., day 5), whereas it is barely expressed in the granulopoietic pathway. In the first series of functional studies, HPCs were treated with antisense oligomers targeted to transcription factor mRNA: inhibition of GATA-2 expression caused a decreased number of both erythroid and granulocyte-monocytic clones, whereas inhibition of NF-E2 or GATA-1 expression induced a selective impairment of erythroid colony formation. In a second series of functional studies, HPCs treated with retinoic acid were induced to shift from erythroid to granulocytic differentiation (Labbaye et al. 1994. Blood. 83:651656); this was coupled with abrogation of GATA-1, NF-E2, and EpR expression and conversely enhanced GATA-2 levels. These results indicate the expression and key role of GATA-2 in the early stages of HPC proliferation/differentiation. Conversely, NF-E2 and GATA-1 expression and function are apparently restricted to erythroid differentiation and maturation: their expression precedes that of the EpR, and their function may be in part mediated via the EpR.

Original languageEnglish
Pages (from-to)2346-2358
Number of pages13
JournalJournal of Clinical Investigation
Volume95
Issue number5
Publication statusPublished - 1995

Fingerprint

Hematopoiesis
Hematopoietic Stem Cells
Erythropoietin Receptors
Messenger RNA
Transcription Factors
GATA Transcription Factors
Growth Differentiation Factors
Tretinoin
Granulocytes
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Proteins
Clone Cells
Cell Proliferation

Keywords

  • hematopoiesis
  • progenitor cell
  • transcription factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Labbaye, C., Valtieri, M., Barberi, T., Meccia, E., Masella, B., Pelosi, E., ... Peschle, C. (1995). Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. Journal of Clinical Investigation, 95(5), 2346-2358.

Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. / Labbaye, C.; Valtieri, M.; Barberi, T.; Meccia, E.; Masella, B.; Pelosi, E.; Condorelli, G. L.; Testa, U.; Peschle, C.

In: Journal of Clinical Investigation, Vol. 95, No. 5, 1995, p. 2346-2358.

Research output: Contribution to journalArticle

Labbaye, C, Valtieri, M, Barberi, T, Meccia, E, Masella, B, Pelosi, E, Condorelli, GL, Testa, U & Peschle, C 1995, 'Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis', Journal of Clinical Investigation, vol. 95, no. 5, pp. 2346-2358.
Labbaye C, Valtieri M, Barberi T, Meccia E, Masella B, Pelosi E et al. Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. Journal of Clinical Investigation. 1995;95(5):2346-2358.
Labbaye, C. ; Valtieri, M. ; Barberi, T. ; Meccia, E. ; Masella, B. ; Pelosi, E. ; Condorelli, G. L. ; Testa, U. ; Peschle, C. / Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 5. pp. 2346-2358.
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