Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation
Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation
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DOI：
10.1126/science.aag3145
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发表时间：
2016-12-02
期刊：
影响因子：
56.9
通讯作者：
Yamazaki, Satoshi
中科院分区：
文献类型：
--
作者：
Taya, Yuki;Ota, Yasunori;Yamazaki, Satoshi
一个特殊的骨髓微环境(NICE)调节造血干细胞(HSC)的自我更新和承诺。对于成功的供者-HSC移植，必须通过清髓性放疗或化疗来清空骨灰龛。然而，清髓手术可能会导致严重的并发症，甚至死亡。在此，我们报道了必需的氨基酸--缬氨酸对于HSCs的增殖和维持是不可或缺的。小鼠和人的HSCs在缺乏缬氨酸的条件下培养时都不能增殖。在喂食限制缬氨酸饮食的小鼠中，HSC频率在1周内显著下降。此外，限制饮食中的Valine排空了小鼠的骨髓，并提供了供者-HSC植入，而不需要化疗照射的骨髓清除术。这些发现表明Valine在HSC维持中的关键作用，并提示限制饮食Valine可能会减少HSC移植中的医源性并发症。
A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. These findings indicate a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation.