生物
胚胎
胚胎干细胞
炎症
祖细胞
免疫学
单核细胞
骨髓
CX3CR1型
人口
男科
细胞生物学
抛物线性
归巢(生物学)
干细胞
医学
趋化因子
遗传学
趋化因子受体
基因
环境卫生
生态学
作者
Kaaweh Molawi,Yochai Wolf,Prashanth K. Kandalla,Jérémy Favret,Nora Hagemeyer,Kathrin Frenzel,Alexander R. Pinto,Kay Klapproth,Sandrine Henri,Bernard Malissen,Hans-Reimer Rodewald,Nadia Rosenthal,Marc Bajénoff,Marco Prinz,Steffen Jung,Michael H. Sieweke
摘要
Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1+ cMΦ diversifies into MHCII+ and MHCII− cells. Genetic fate mapping demonstrated that cMΦ derived from CX3CR1+ embryonic progenitors persisted into adulthood but the initially high contribution to resident cMΦ declined after birth. Consistent with this, the early significant proliferation rate of resident cMΦ decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMΦ populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMΦ. Together, our observations indicate that in the heart, embryo-derived cMΦ show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.
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