Adult T-cell progenitors retain myeloid potential
Adult T-cell progenitors retain myeloid potential
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DOI：
10.1038/nature06839
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发表时间：
2008-04-10
期刊：
影响因子：
64.8
通讯作者：
Kawamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Wada, Haruka;Masuda, Kyoko;Kawamoto, Hiroshi
在造血过程中，多能造血干细胞被顺序限制以产生各种谱系定向祖细胞。造血的经典模型假定，在分化的第一步，干细胞产生共同的骨髓-红系祖细胞和共同的淋巴样祖细胞（CLP）。然而，我们之前在胎鼠中的研究表明，即使谱系分支向T和B细胞分离，髓样潜能也持续存在（1-6）。因此，我们提出了造血的“骨髓为基础的”模型（7，8），其中干细胞最初产生共同的骨髓-红细胞祖细胞和共同的骨髓-淋巴祖细胞。T细胞和B细胞祖细胞随后分别通过髓样T和髓样B阶段从常见的骨髓淋巴祖细胞产生。然而，目前尚不清楚这种基于骨髓的模型是否也适用于成人造血。在这里，我们提供了克隆的证据表明，在成人胸腺中的早期细胞群包含祖细胞，已经失去了产生B细胞的潜力，但保留大量的巨噬细胞的潜力，以及T细胞，自然杀伤（NK）细胞和树突状细胞的潜力。我们还表明，这种T细胞祖细胞可以在体内胸腺环境中产生巨噬细胞。我们的研究结果反对经典的二分法模型，其中T细胞来源于CLP，相反，他们支持的有效性的“骨髓为基础的”成人和胎儿造血模型。
During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells(1-6). We therefore proposed the 'myeloid-based' model of haematopoiesis(7,8), in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the 'myeloid-based' model for both adult and fetal haematopoiesis.