A critical role for PU.1 in homing and long-term engraftment by hematopoietic stem cells in the bone marrow
A critical role for PU.1 in homing and long-term engraftment by hematopoietic stem cells in the bone marrow
复制标题
DOI：
10.1182/blood.v94.4.1283.416k16_1283_1290
复制
发表时间：
1999-08-15
期刊：
影响因子：
20.3
通讯作者：
Scott, EW
中科院分区：
文献类型：
--
作者：
Fisher, RC;Lovelock, JD;Scott, EW
我们以前已经证明，PU.1是所需的生产淋巴和骨髓，但不是红系祖细胞在胎儿肝脏。在这项研究中，竞争性重建试验表明，E14.5 PU.1（-/-）造血祖细胞（HPC）不能维持永久/成人红细胞生成或有助于淋巴和骨髓谱系。PU.1（-/-）HPC不能协同响应促红细胞生成素和干细胞因子，并具有减少的c-kit表达，这可能解释红细胞缺陷。将标记的PU.1（-/-）、AA4.1（+）胎肝HPC转移到辐射受体中，在那里它们表现出严重受损的归巢和定殖骨髓的能力。发现PU.1-/- HPC缺乏整合素α（4）（VLA-4/CD 49 d）、α（5）（VLA-5/CD 49 e）和CD 11b（α（M））。总的来说，这项研究表明，PU.1在控制造血祖细胞向骨髓的迁移和建立长期多系造血中起着重要作用，（C）1999年由美国血液学会。
We have previously demonstrated that PU.1 is required for the production of lymphoid and myeloid, but not of erythroid progenitors in the fetal liver. In this study, competitive reconstitution assays show that E14.5 PU.1(-/-) hematopoietic progenitors (HPC) fail to sustain definitive/adult erythropoiesis or to contribute to the lymphoid and myeloid lineages. PU.1(-/-) HPC are unable to respond synergistically to erythropoietin plus stem cell factor and have reduced expression of c-kit, which may explain the erythroid defect. Fluorescently labeled, PU.1(-/-), AA4.1(+), fetal liver HPC were transferred into irradiated recipients, where they demonstrated a severely impaired ability to home to and colonize the bone marrow. PU.1-/- HPC were found to lack integrins alpha(4) (VLA-4/CD49d), alpha(5) (VLA-5/CD49e), and CD11b (alpha(M)). Collectively, this study has shown that PU.1 plays an important role in controlling migration of hematopoietic progenitors to the bone marrow and the establishment of long-term multilineage hematopoiesis, (C) 1999 by The American Society of Hematology.