Macrophages with different origins proliferate ex vivo and do not lose their core intrinsic features.

Macrophages are maintained by bone marrow (BM)-derived monocytes, but macrophages originating from fetal liver (FL) or yolk sac (YS) persist in many adult tissues due to their higher proliferative capacity. Here, we report useful models of macrophages with different origins. We expanded macrophages from mouse BM, FL, or YS through long-term culture. They proliferated with M-CSF, and YS lines were the fastest and survived without M-CSF for a longer period. YS and FL lines were more resistant to apoptotic cell death and similar in gene expression/chromatin accessibility, whereas YS and BM lines exhibited the most distinct profiles. When transplanted into mice, YS line expressed markers lost during the culture. BM, FL, and YS lines appear to maintain differences in intrinsic proliferation/anti-apoptosis/survival capacities and can restore phenotypes lost during the culture by in vivo transfer. Our models help in the understanding of physiological/pathological roles of macrophages with different origins.