Hematopoietic stem cells (HSCs) are typically characterized by transplantation into irradiated hosts in a highly perturbed microenvironment. Here, we show that selective and temporally controlled depletion of resident HSCs through genetic deletion of Gata2 constitutes efficient recipient conditioning for transplantation without irradiation. Strikingly, we achieved robust engraftment of donor HSCs even when delaying Gata2 deletion until 4 weeks after transplantation, allowing homing and early localization to occur in a completely non-perturbed environment. When HSCs from the congenic strains Ly5.1 and Ly5.2 were competitively transplanted, we found that the more proliferative state of Ly5.2 HSCs was associated with superior long-term engraftment when using conditioning by standard irradiation, while higher CXCR4 expression and a better homing ability of Ly5.1 HSCs strongly favored the outcome in our inducible HSC depletion model. Thus, the mode and timing of recipient conditioning challenges distinct functional features of transplanted HSCs.

造血干细胞 (HSC) 的典型特征是在高度扰动的微环境中移植到受照射的宿主中。在这里，我们表明，通过Gata2的基因缺失对常驻 HSCs 进行选择性和时间控制的消耗构成了无辐射移植的有效受体调节。引人注目的是，即使在延迟Gata2的情况下，我们也实现了供体 HSC 的稳健植入删除直到移植后 4 周，允许在完全不受干扰的环境中进行归巢和早期定位。当来自同类菌株 Ly5.1 和 Ly5.2 的 HSCs 竞争性移植时，我们发现 Ly5.2 HSCs 的更多增殖状态与使用标准照射条件下的长期植入有关，而更高的 CXCR4 表达和Ly5.1 HSC 更好的归巢能力强烈支持我们的诱导型 HSC 耗竭模型的结果。因此，受体调节的模式和时间挑战移植的 HSC 的不同功能特征。