<scp>USP</scp>
            18 lack in microglia causes destructive interferonopathy of the mouse brain

Goldmann, Tobias; Zeller, Nicolas; Raasch, Jenni; Kierdorf, Katrin; Frenzel, Kathrin; Ketscher, Lars; Basters, Anja; Staszewski, Ori; Brendecke, Stefanie M.; Spieß, Alena; Tay, Tuan Leng; Kreutz, Clemens; Timmer, Jens; Mancini, Grazia M.S.; Blank, Thomas; Fritz, Günter; Biber, Knut; Lang, Roland; Malo, Danielle; Merkler, Doron; Heikenwälder, Mathias; Knobeloch, Klaus–Peter; Prinz, Marco

doi:10.15252/embj.201490791

Cited by 172 publications

(171 citation statements)

References 63 publications

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“…1 B ); the retention of some of these ohnologs may be driven by immune pathway regulation. Figure 4 A depicts a snapshot of the evolutionary emergence of immune genes—as is evident WGD has been responsible for generation most of the components of the antiviral pathway as well as the UPS components regulating it, such as DUBs USP18(Goldmann et al. 2015), USP4(Wada et al.…”

Section: Resultsmentioning

confidence: 99%

The Evolution and Functional Diversification of the Deubiquitinating Enzyme Superfamily

Vlasschaert

Cook

Xia

et al. 2017

Genome Biology and Evolution

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Ubiquitin and ubiquitin-like molecules are attached to and removed from cellular proteins in a dynamic and highly regulated manner. Deubiquitinating enzymes are critical to this process, and the genetic catalogue of deubiquitinating enzymes expanded greatly over the course of evolution. Extensive functional redundancy has been noted among the 93 members of the human deubiquitinating enzyme (DUB) superfamily. This is especially true of genes that were generated by duplication (termed paralogs) as they often retain considerable sequence similarity. Because complete redundancy in systems should be eliminated by selective pressure, we theorized that many overlapping DUBs must have significant and unique spatiotemporal roles that can be evaluated in an evolutionary context. We have determined the evolutionary history of the entire class of deubiquitinating enzymes, including the sequence and means of duplication for all paralogous pairs. To establish their uniqueness, we have investigated cell-type specificity in developmental and adult contexts, and have investigated the coemergence of substrates from the same duplication events. Our analysis has revealed examples of DUB gene subfunctionalization, neofunctionalization, and nonfunctionalization.

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Section: Resultsmentioning

confidence: 99%

The Evolution and Functional Diversification of the Deubiquitinating Enzyme Superfamily

Vlasschaert

Cook

Xia

et al. 2017

Genome Biology and Evolution

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“…RT–PCRs were performed as described recently 43 . The extracted RNA (1μg per sample) was transcribed into cDNA using the High Capacity RNA-to-cDNA Kit (Life Technologies) following the provided protocol.…”

Section: Methodsmentioning

confidence: 99%

Origin, fate and dynamics of macrophages at central nervous system interfaces

et al. 2016

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Perivascular, meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It has been assumed that they have a high turnover with blood-borne monocytes. However, large scale single-cell RNA-sequencing reveals a striking molecular overlap between perivascular macrophages and microglia but not monocytes. Using several fate mapping approaches and parabiosis we demonstrate that CNS macrophages arise from yolk sac precursors during embryonic development and remain a stable population. Notably, the generation of CNS macrophages relies on the transcription factor Pu.1 whereas myb, Batf3 and Nr4a1 are not required. Upon autoimmune inflammation, macrophages undergo extensive self-renewal by local proliferation. Our data provide challenging new insights into brains innate immune system.

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“…Ubiquitin-specific protease 18 (USP18) was recently found to be a critical negative regulator of microglial activation, especially in white matter microglia (112). Loss of USP18 induces an overactivated phenotype in resting microglia and severe CNS pathology.…”

Section: R E V I E W S E R I E S : G L I a A N D N E U R O D E G E Nmentioning

confidence: 99%