{Reference Type}: Journal Article
{Title}: Hypoxia drives HIF2-dependent reversible macrophage cell cycle entry.
{Author}: Meng B;Zhao N;Mlcochova P;Ferreira IATM;Ortmann BM;Davis T;Wit N;Rehwinkel J;Cook S;Maxwell PH;Nathan JA;Gupta RK;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 7
{Year}: 2024 Jul 23
暂无{DOI}: 10.1016/j.celrep.2024.114471
{Abstract}: 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.