Fig. 4: Although microglia are able to engulf microglial debris in vitro, territory-dependent competition hinders microglia-to-microglial debris engulfment in vivo. | Nature Communications

Fig. 4: Although microglia are able to engulf microglial debris in vitro, territory-dependent competition hinders microglia-to-microglial debris engulfment in vivo.

From: Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice

Fig. 4

a Scheme of tamoxifen-triggered sparse labeling of microglia for investigation of the microglial engulfment capacity of microglial debris in CX3CR1-CreER::Ai14 and P2Y12-CreER-GFP::Ai14 mice. b tdTomato- microglia do not engulf tdTomato+ microglial debris under physiological conditions (D30) or upon CSF1R inhibition (D32) in CX3CR1-CreER::Ai14 mice. c Quantification of the tdTomato+ microglial percentage in CX3CR1-CreER::Ai14 mice. N = 5 mice for each group. Two-tailed independent t test. d tdTomato- microglia do not engulf tdTomato+ microglial debris under physiological conditions (D20) or upon CSF1R inhibition (D22) in P2Y12-CreER-GFP::Ai14 mice. e Quantification of the tdTomato+ microglial percentage in P2Y12-CreER-GFP::Ai14 mice. N = 4 mice for each group. Two-tailed independent t test. f Quantification of tdTomato+ microglial debris engulfment by microglia and astrocytes under physiological conditions. The data from the microglial group were adjusted based on the sparse labeling percentage at D30 (CX3CR1-CreER::Ai14) and D20 (P2Y12-CreER-GFP::A14). The data from the astrocytes are obtained from the cortex results shown in Fig. 3c. N = 5 CX3CR1-CreER::Ai14 mice, N = 4 P2Y12-CreER-GFP::Ai14 mice and N = 6 ALDH1L1-CreER::Ai14 mice. One-way ANOVA with Holm‒Sidak’s multiple comparisons test (post hoc). g Scheme of the in vitro assay of microglia-to-microglial debris engulfment using pHrodo-labeled microglial debris. h IBA1+ microglia engulf pHrodo-labeled microglial debris in the cell culture. pHrodo is illustrated by the green pseudocolor for better visualization. i Quantification of the microglia-to-microglial debris engulfment after exposure to pHrodo-labeled microglial debris for 24 h. N = 4 biological replicates of each group. Two-tailed independent t test. j The territory-dependent competition model (hypothesis) explains that microglia do not phagocytose microglial debris in vivo. (I) Under normal conditions and (II) when a microglial cell dies. PLX5622: PLX5622-formulated AIN-76A diet; IP intraperitoneal. Data are presented as mean ± SD. The source data are provided as a Source Data file.

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