RELEASE OF EARLY HUMAN HEMATOPOIETIC PROGENITORS FROM QUIESCENCE BY ANTISENSE TRANSFORMING GROWTH FACTOR-BETA-1 OR RB-OLIGONUCLEOTIDES

被引：218

作者：

HATZFELD, J ^{[1
]}

LI, ML ^{[1
]}

BROWN, EL ^{[1
]}

SOOKDEO, H ^{[1
]}

LEVESQUE, JP ^{[1
]}

OTOOLE, T ^{[1
]}

GURNEY, C ^{[1
]}

CLARK, SC ^{[1
]}

HATZFELD, A ^{[1
]}

机构：

[1] GENET INST, CAMBRIDGE, MA 02140 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 1991年 / 174卷 / 04期

关键词：

D O I：

10.1084/jem.174.4.925

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：925 / 929

页数：5

共 23 条

[11] REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION BY THE PRODUCT OF THE RETINOBLASTOMA-SUSCEPTIBILITY GENE [J].