低氧条件（缺氧）主要与分裂细胞的细胞周期停滞有关。巨噬细胞通常在 G0 期处于静止状态，但可以响应组织信号而增殖。在这里，我们表明缺氧（1% 氧张力）会导致巨噬细胞可逆地进入细胞周期。细胞周期进展主要限于G0-G1/S阶段转变，很少进展至G2/M。这种细胞周期转变是由 HIF2α 指导的转录程序触发的。这种反应伴随着细胞周期相关蛋白表达的增加，其中包括 CDK1，已知 CDK1 会在 T592 位点磷酸化 SAMHD1，从而调节抗病毒活性。脯氨酰羟化酶 (PHD) 抑制剂能够重现巨噬细胞中 HIF2α 依赖性细胞周期进入。最后，肺癌中的肿瘤相关巨噬细胞（TAM）表现出转录组谱，代表单细胞水平上对低氧和细胞周期进展的反应。这些发现对低氧环境常见的炎症和肿瘤进展/转移具有影响。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Low-oxygen conditions (hypoxia) have been associated primarily with cell-cycle arrest in dividing cells. Macrophages are typically quiescent in G0 but can proliferate in response to tissue signals. Here we show that hypoxia (1% oxygen tension) results in reversible entry into the cell cycle in macrophages. Cell cycle progression is largely limited to G0-G1/S phase transition with little progression to G2/M. This cell cycle transitioning is triggered by an HIF2α-directed transcriptional program. The response is accompanied by increased expression of cell-cycle-associated proteins, including CDK1, which is known to phosphorylate SAMHD1 at T592 and thereby regulate antiviral activity. Prolyl hydroxylase (PHD) inhibitors are able to recapitulate HIF2α-dependent cell cycle entry in macrophages. Finally, tumor-associated macrophages (TAMs) in lung cancers exhibit transcriptomic profiles representing responses to low oxygen and cell cycle progression at the single-cell level. These findings have implications for inflammation and tumor progression/metastasis where low-oxygen environments are common.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.