[INTRODUCTION] Microglia are brain-resident macrophages that carry out immune surveillance, support neurogenesis and neuronal survival, shape the neuronal network, and maintain tissue homeostasis (Nimmerjahn et al., 2005; Hanisch and Kettenmann, 2007; Sierra et al., 2010; Tremblay et al., 2010; Schafer et al., 2012; Ueno et al., 2013; Squarzoni et al., 2014; Schafer and Stevens, 2015; Diaz-Aparicio et al., 2020). The adult resident pool of microglia is primarily derived from yolk sac (YS) erythromyeloid progenitors (EMPs) that have clonally proliferated within the brain parenchyma during development (Alliot et al., 1999; Ginhoux et al., 2010; Hashimoto et al., 2013; Gomez Perdiguero et al., 2015). To maintain their cell density in adulthood, the resident microglial cells undergo local clonal self-renewal (Ajami et al., 2007; Askew et al., 2017; Réu et al., 2017; Tay et al., 2017). A study on parabiotic chimeric mice revealed that the resident microglial population is exclusively replenished by locally derived microglial clones with no evidence of contribution from peripheral myeloid progenitors (Ajami et al., 2007). Clonal expansion of non-ablated residual microglia was also found to be responsible for re-establishing steady state microglial cell densities following a pharmacological ablation (Huang et al., 2018). Homeostatic microglia continuously monitor the brain environment, scavenge dying cells and cellular debris, and rapidly respond to any tissue damage (Kreutzberg, 1996; Streit et al., 1999). In response to acute pathology, resident microglia rapidly accumulate around the lesion via clonal microgliosis (Streit et al., 1999; Ladeby et al., 2005; Ajami et al., 2007; Ransohoff, 2007). Microgliosis at the site of CNS damage has been shown to be governed by signaling molecules like colony-stimulating factor-1 (CSF1), fractalkine receptor (CX3CR1) and purinergic receptor P2Y12 (P2RY12) (Guan et al., 2016; Gu et al., 2016; Peng et al., 2016). To repair damage, microglia elicit proinflammatory cytokines and ...