The Hedgehog receptor Patched controls lymphoid lineage commitment
The Hedgehog receptor Patched controls lymphoid lineage commitment
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DOI：
10.1182/blood-2007-02-075648
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Hahn, Heidi
中科院分区：
文献类型：
--
作者：
Uhmann, Anja;Dittmann, Kai;Hahn, Heidi
造血的第一步是确定骨髓中多能祖细胞的淋巴系和髓系。在成年小鼠中使用有条件的消融策略，我们发现这一分化步骤需要Hedgehog(HH)的细胞表面结合受体Patted(PTCH)。在缺乏PTCH的情况下，T和B淋巴系的发展被阻止在骨髓中共同淋巴祖细胞的水平上。因此，外周T和B细胞的产生被取消。在ptch突变小鼠中，髓系细胞发育正常。最后，过继转移实验证实，基质细胞室是淋巴系与髓系承诺的关键依赖于PTCH的诱导物。我们的数据显示，PTCH在成年机体中扮演着适当多样化造血干细胞的主开关的角色。
A first step in hematopoiesis is the specification of the lymphoid and myeloid lineages from multipotent progenitor cells in the bone marrow. Using a conditional ablation strategy in adult mice, we show that this differentiation step requires Patched (Ptch), the cell surface-bound receptor for Hedgehog (Hh). In the absence of Ptch, the development of T- and B-lymphoid lineages is blocked at the level of the common lymphoid progenitor in the bone marrow. Consequently, the generation of peripheral T and B cells is abrogated. Cells of the myeloid lineage develop normally in Ptch mutant mice. Finally, adoptive transfer experiments identified the stromal cell compartment as a critical Ptch-dependent inducer of lymphoid versus myeloid lineage commitment. Our data show that Ptch acts as a master switch for proper diversification of hematopoietic stem cells in the adult organism.