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Updated: Jun 15, 2025
Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
Macrophages with different origins proliferate ex vivo and do not lose their core intrinsic features
Sara A Habash1,2, Naofumi Takahashi1, Youssef M Eltalkhawy1
1Division of Infection & Hematopoiesis, Kumamoto University, Kumamoto, Japan.
Abstract:
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.
Insights
Macrophages from different origins, like fetal liver (FL) and yolk sac (YS), show distinct survival and proliferation capabilities. These models aid in understanding macrophage roles in health and disease.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Macrophages are crucial immune cells with diverse origins, including bone marrow (BM), fetal liver (FL), and yolk sac (YS).
- Macrophages derived from FL and YS exhibit greater proliferative capacity and persist longer in adult tissues compared to BM-derived counterparts.
- Understanding the distinct properties of macrophages based on their origin is essential for comprehending their physiological and pathological roles.
Purpose of the Study:
- To establish and characterize macrophage models derived from distinct embryonic origins (BM, FL, YS).
- To investigate the proliferative capacity, survival mechanisms, and gene expression profiles of these macrophage models.
- To assess the ability of these macrophage models to restore lost phenotypes after in vivo transfer.
Main Methods:
- Long-term culture of mouse macrophages derived from BM, FL, and YS using M-CSF.
- Assessment of proliferation rates, survival without M-CSF, and resistance to apoptotic cell death.
- Analysis of gene expression and chromatin accessibility.
- In vivo transplantation experiments to evaluate phenotype restoration.
Main Results:
- YS-derived macrophages demonstrated the fastest proliferation and longest survival without M-CSF.
- YS and FL macrophages showed increased resistance to apoptosis compared to BM-derived macrophages.
- YS and BM macrophage lines exhibited the most distinct gene expression and chromatin accessibility profiles.
- Transplanted YS macrophages restored markers lost during culture, indicating in vivo phenotype recovery.
Conclusions:
- Macrophage models derived from BM, FL, and YS exhibit intrinsic differences in proliferation, anti-apoptosis, and survival capacities.
- These distinct macrophage populations can restore lost phenotypes upon in vivo transfer, highlighting their plasticity.
- The developed models provide valuable tools for studying the diverse functions of macrophages in various physiological and pathological contexts.
