Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides.
Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides.
复制标题
通过反义转化生长因子β1或RB寡核苷酸从静止中释放早期人造血祖细胞。
DOI：
10.1084/jem.174.4.925
复制
发表时间：
1991-10-01
影响因子：
15.3
通讯作者：
Hatzfeld, A
中科院分区：
文献类型：
--
作者：
Hatzfeld, J;Li, M L;Brown, E L;Sookdeo, H;Levesque, J P;O'Toole, T;Gurney, C;Clark, S C;Hatzfeld, A
我们利用反义寡核苷酸研究了转化生长因子β (tgf - β)和两个反基因视网膜母细胞瘤易感性（Rb）和p53在培养早期造血细胞增殖负调控中的作用。反义tgf - β序列显著提高了多系、早期红系和肉芽单胞祖细胞的集落形成频率，但对晚期祖细胞的集落形成没有影响。单细胞培养和极限稀释分析表明，自分泌tgf - β是由早期祖细胞亚群产生的。反义Rb而非反义p53在释放多潜能祖细胞（集落形成单位-粒细胞/红细胞/巨噬细胞/巨核细胞）方面具有相似的结果。Rb反义能部分逆转外源性tgf - β的抑制作用。抗tgf - β阻断抗体、反义tgf - β或Rb寡核苷酸都有类似的效果。当这些试剂联合使用时，没有观察到加性效应，表明有共同的作用途径。我们的结果与tgf - β的自分泌产生通过与Rb基因产物相互作用负性调节早期造血祖细胞循环状态的模型一致。
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.