de Vries P, Brasel K A, McKenna H J, Williams D E, Watson J D
Department of Experimental Hematology, Immunex Corporation, Seattle, Washington 98101.
J Exp Med. 1992 Dec 1;176(6):1503-9. doi: 10.1084/jem.176.6.1503.
The introduction of clonal assays and long-term culture systems has resulted in considerable progress in the understanding of the early events that control self-renewal and commitment to differentiation of pluripotent hematopoietic stem cells (PHSC). Relatively little is known about the factors that control the commitment of PHSC to the lymphoid lineages, especially the T cell lineage. In the present study, the expression of the proto-oncogene c-kit was used to isolate and study the capacity of highly purified day 14 colony-forming units-spleen (CFU-S) to reconstitute the thymus of sublethally irradiated Thy-1 congenic recipient mice. We demonstrate here that one c-kit positive (c-kitpos) stem cell upon intrathymic transfer can effectively reconstitute the thymus of a sublethally irradiated recipient. After a lag phase of 15 d, high levels of donor-derived thymocytes (Thy-1.1pos) could be detected until 65 d after transplantation in Thy-1.2pos host mice. Donor-derived cells were only detected in the lobe of the thymus in which cells were previously injected and not in the noninjected lobe. These data suggest that c-kitpos stem cells do not migrate from one lobe to another and that they do not re-seed the thymus after having migrated to the bone marrow. The level and duration of reconstitution was found to be cell dose dependent, suggesting that, over time, endogenous stem cells compete with donor stem cells for available sites in the thymus microenvironment. The data presented in this paper demonstrate that commitment of purified adult bone marrow-derived c-kitpos stem cells to the T cell differentiation pathway can occur in the thymus and does not have to happen in the bone marrow.
克隆分析和长期培养系统的引入，在理解控制多能造血干细胞（PHSC）自我更新和分化的早期事件方面取得了相当大的进展。对于控制PHSC向淋巴系，尤其是T细胞系分化的因素，人们了解得相对较少。在本研究中，原癌基因c-kit的表达被用于分离和研究高度纯化的第14天脾集落形成单位（CFU-S）重建造血亚致死剂量照射的Thy-1同基因受体小鼠胸腺的能力。我们在此证明，一个c-kit阳性（c-kitpos）干细胞经胸腺内移植后可有效重建造血亚致死剂量照射受体的胸腺。经过15天的延迟期后，在Thy-1.2pos宿主小鼠中，移植后65天之前均可检测到高水平的供体来源胸腺细胞（Thy-1.1pos）。供体来源的细胞仅在先前注射细胞的胸腺叶中被检测到，而在未注射的叶中未被检测到。这些数据表明，c-kitpos干细胞不会从一个叶迁移到另一个叶，并且它们迁移到骨髓后不会重新定植到胸腺。重建造血的水平和持续时间被发现是细胞剂量依赖性的，这表明随着时间的推移，内源性干细胞与供体干细胞竞争胸腺微环境中的可用位点。本文提供的数据表明，纯化的成年骨髓来源的c-kitpos干细胞向T细胞分化途径的分化可在胸腺中发生，而不必在骨髓中发生。
