Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation
Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation
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DOI：
10.1182/blood-2005-08-3454
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Pear, WS
中科院分区：
文献类型：
--
作者：
Maillard, I;Schwarz, BA;Pear, WS
早期 T 谱系祖细胞 (ETP) 在多能骨髓祖细胞定植胸腺后出现。尽管可能存在替代的 T 细胞分化途径，但 ETP 可能充当成年小鼠 T 细胞发育的生理祖细胞。当我们研究骨髓移植 (BMT) 后 T 细胞重建的机制时，我们发现在 ETP 池得到补充之前就发生了有效的供体来源的胸腺生成。同时，T谱系限制性祖细胞在胸腺外部位产生，包括在脾脏和周围淋巴结中，但不在骨髓或肝脏中。这些T谱系定型细胞的产生是通过Notch依赖性分化过程发生的。多能骨髓祖细胞有效地产生胸腺外T谱系定向细胞，而普通淋巴祖细胞却不能。我们的数据显示了 BMT 后环境中 T 谱系定型位点的可塑性，并表明来自多能祖细胞的 Notch 驱动的胸腺外 T 谱系定型可能有助于 BMT 后的早期 T 谱系重建。
Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage-restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage-committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage-committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic T-lineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT.