Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides.
J Exp Med
; 174(4): 925-9, 1991 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-1717634
ABSTRACT
We have used antisense oligonucleotides to study the roles of transforming growth factor beta (TGF-beta) and the two antioncogenes, retinoblastoma susceptibility (Rb) and p53, in the negative regulation of proliferation of early hematopoietic cells in culture. The antisense TGF-beta sequence significantly enhanced the frequency of colony formation by multi-lineage, early erythroid, and granulomonocytic progenitors, but did not affect colony formation by late progenitors. Single cell culture and limiting dilution analysis indicated that autocrine TGF-beta is produced by a subpopulation of early progenitors. Antisense Rb but not antisense p53 yielded similar results in releasing multipotential progenitors (colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte) from quiescence. Rb antisense could partially reverse the inhibitory effect of exogenous TGF-beta. Anti-TGF-beta blocking antibodies, antisense TGF-beta, or Rb oligonucleotides all had similar effects. No additive effects were observed when these reagents were combined, suggesting a common pathway of action. Our results are consistent with the model that autocrine production of TGF-beta negatively regulates the cycling status of early hematopoietic progenitors through interaction with the Rb gene product.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tionucleotídeos
/
Células-Tronco Hematopoéticas
/
Divisão Celular
/
Genes p53
/
Genes do Retinoblastoma
/
Oligonucleotídeos Antissenso
/
Fator de Crescimento Transformador beta
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
1991
Tipo de documento:
Article
País de afiliação:
França