Surviving microglia and nonmicroglial progenitors contribute to microglial repopulation following colony-stimulating factor 1 receptor inhibition.

IF 2.1 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2026-08-12 Epub Date: 2026-07-08 DOI:10.1097/WNR.0000000000002286

Eric Yuhsiang Wang, Hank Szuhan Chen, Ya Lan Yang, Ching Mei Wu, Yi-Wen Chang, Ted Weita Lai

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引用次数: 0

Abstract

Background: Microglial repopulation after depletion via colony-stimulating factor 1 receptor (CSF1R) inhibition holds therapeutic potential for neurological disorders, but the cellular sources remain debated. We investigated whether repopulation arises solely from surviving microglia or also from nonmicroglial progenitors.

Methods: Using Cx3cr1 CreER :Ai14 (tdTomato) reporter mice, we labeled microglia before PLX3397-induced depletion and assessed repopulation. Next, in Cx3cr1 CreER+/- :Csf1r fl/fl mice, we combined tamoxifen-induced genetic CSF1R deletion with PLX3397 to ablate microglia completely and evaluated recovery.

Results: We found that repopulated microglia were predominantly tdTomato + , indicating derivation from surviving Cx3cr1 + microglia. Combined tamoxifen and PLX3397 achieved near-complete ablation, yet microglia repopulated and were re-depletable by PLX3397, confirming potential nonmicroglial origins.

Conclusion: Microglial repopulation primarily involves proliferation of surviving microglia but can recruit nonmicroglial progenitors when depletion is exhaustive. These insights resolve prior inconsistencies and guide therapeutic strategies for microglial replacement treatment.

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存活的小胶质细胞和非小胶质细胞祖细胞在集落刺激因子1受体抑制后有助于小胶质细胞的再生。

背景：通过集落刺激因子1受体（CSF1R）抑制消耗后的小胶质细胞再生具有治疗神经系统疾病的潜力，但细胞来源仍存在争议。我们研究了再生是否仅来自存活的小胶质细胞或也来自非小胶质细胞祖细胞。方法：使用Cx3cr1CreER:Ai14 （tdTomato）报告小鼠，我们在plx3397诱导耗尽前标记小胶质细胞并评估其再种群。接下来，在Cx3cr1CreER+/-:Csf1rfl/fl小鼠中，我们将他莫昔芬诱导的CSF1R基因缺失与PLX3397联合使用，以完全切除小胶质细胞并评估恢复情况。结果：我们发现重新填充的小胶质细胞主要是tdTomato+，表明来源于存活的Cx3cr1+小胶质细胞。他莫昔芬和PLX3397联合治疗几乎完全消融，但PLX3397可使小胶质细胞重新填充并重新消耗，证实了潜在的非小胶质细胞起源。结论：小胶质细胞的再生主要涉及存活小胶质细胞的增殖，但当耗尽耗尽时可以招募非小胶质细胞祖细胞。这些见解解决了先前的不一致，并指导了小胶质细胞替代治疗的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.