New tools for studying microglia in the mouse and human CNS (original) (raw)

“…In the acute phase (day 1), microglia have a proinflammatory phenotype, yet this response was transient, as the majority phenotypes after ICH or find evidence that astrocytes respond to TGF-β1 at 14 days after ICH, it is possible that astrocytes provide the early source of TGF-β1 that initiates the phenotype modulation in microglia. We used the CD45 int CD11b + classification of microglia in WT mice (51)(52)(53), which matched the high CX3CR1 expression in microglia from our BM chimeras and also was recently reported to closely match expression of the microglial marker TMEM119 (9). Our in vitro work relied on primary microglia, eliminating concerns about phenotypic differences observed in immortalized microglial cell lines (8).…”

Section: Discussionmentioning

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“…In the acute phase (day 1), microglia have a proinflammatory phenotype, yet this response was transient, as the majority phenotypes after ICH or find evidence that astrocytes respond to TGF-β1 at 14 days after ICH, it is possible that astrocytes provide the early source of TGF-β1 that initiates the phenotype modulation in microglia. We used the CD45 int CD11b + classification of microglia in WT mice (51)(52)(53), which matched the high CX3CR1 expression in microglia from our BM chimeras and also was recently reported to closely match expression of the microglial marker TMEM119 (9). Our in vitro work relied on primary microglia, eliminating concerns about phenotypic differences observed in immortalized microglial cell lines (8).…”

Section: Discussionmentioning

“…Microglia develop independently of the transcription factor c-Myb and hematopoietic stem cells (5,6) but are dependent upon the transcription factors IRF8 and PU.1 (7). Microglia also have a unique molecular signature that is distinct from that of bloodderived macrophages (8,9). These signatures indicate that microglia and blood-derived macrophages likely play distinct roles in disease pathogenesis and recovery -hence the need to study these populations independently.…”

Section: Introductionmentioning

“…However, following microglial replacement, this microglial‐associated CD68 expression was significantly reduced ( p < 0.001, Figure 2h). As resident microglia share expression of IBA1 with peripherally‐derived macrophages, we also conducted additional immunohistochemical stains using the microglia‐specific markers TMEM119 and P2RY12, which distinguish microglia from peripheral myeloid cells (Bennett et al, 2016). Here, we show that repopulated microglia display high expression of both TMEM119 and P2RY12 (Figure 2k–n), demonstrating that repopulated microglia are indeed resident microglia and do not originate from peripherally‐derived myeloid cells.…”

Section: Resultsmentioning

“…For example, the M1/M2 paradigm does not account for the role of proliferating microglia (37). Furthermore, while transcriptome studies have identified new markers selectively expressed on microglia, including the purinergic receptor P2Y12, transmembrane protein 119 (TMEM119), the chemokine receptor CX3CR1, and Siglec-H, other cell types may also display these markers (38,39). Recently, Grabert and colleagues showed regional microglial heterogeneity in young mice, with the greatest convergence between cerebellar and hippocampal microglia in terms of immunoregulatoryand bioenergetics-related transcripts compared with cortex and striatum.…”

Section: Beyond M1 and M2 Classificationmentioning