Department of Neuroscience, Center for Brain Immunology and Glia (BIG), University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan.
Sci Adv. 2020 Aug 26;6(35):eabb2119. doi: 10.1126/sciadv.abb2119. eCollection 2020 Aug.
Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6C and Ly6C monocytes after tamoxifen dosing and detected a surge of perivascular macrophages before blood-brain barrier breakdown in adult stroke. When dosed by tamoxifen at embryonic day 17 (E17), this method captured fetal hematopoietic cells at E18, subdural Ki67 ameboid cells at postnatal day 2 (P2), and perivascular microglia, leptomeningeal macrophages, and Iba1Tmem119P2RY12 parenchymal microglia in selective brain regions at P24. Furthermore, this fate mapping strategy revealed an acute influx of monocytes after neonatal stroke, which gradually transformed into a ramified morphology and expressed microglial marker genes (Sall1, Tmem119, and P2RY12) for at least 62 days after injury. These results suggest an underappreciated level of monocyte-to-microglia transition in development and after neonatal stroke.
单核细胞是否有助于大脑小胶质细胞在发育过程中或脑损伤后的产生仍存在争议。为了解决这个问题，我们生成了 CCR2-CreER 小鼠，以可诱导的方式追踪单核细胞的衍生物。这种方法在给予他莫昔芬后标记 Ly6C 和 Ly6C 单核细胞，并在成年中风时血脑屏障破裂前检测到血管周巨噬细胞的激增。当在胚胎第 17 天（E17）时给予他莫昔芬时，这种方法在 E18 捕获胎儿造血细胞，在出生后第 2 天（P2）捕获硬膜下 Ki67 阿米巴样细胞，以及在 P24 选择性脑区捕获血管周小胶质细胞、软脑膜巨噬细胞和 Iba1Tmem119P2RY12 实质小胶质细胞。此外，这种命运映射策略揭示了新生儿中风后单核细胞的急性涌入，这些单核细胞逐渐转变为分支形态，并表达小胶质细胞标记基因（Sall1、Tmem119 和 P2RY12），至少在损伤后 62 天。这些结果表明，在发育过程中和新生儿中风后，单核细胞向小胶质细胞的转化程度被低估了。
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