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Brehm, Z.

Publications and source records attributed to Brehm, Z..

2 recordsLinked to original sources

A curated human cellular microRNAome based on 196 primary cell types

BackgroundAn incomplete picture of the expression distribution of microRNAs (miRNAs) across human cell types has long hindered our understanding of this important regulatory class of RNA. With the continued increase in available public small RNA sequencing datasets, there is an opportunity to more fully understand the general distribution of miRNAs at the cell level. ResultsFrom the NCBI Sequence Read Archive, we obtained 6,054 human primary cell datasets and processed 4,184 of them through the miRge3.0 small RNA-seq alignment software. This dataset was curated down, through shared miRNA expression patterns, to 2,077 samples from 196 unique cell types derived from 175 separate studies. Of 2,731 putative miRNAs listed in miRBase (v22.1), 2,452 (89.8%) were detected. Among reasonably expressed miRNAs, 108 were designated as cell specific/near specific, 59 as infrequent, 52 as frequent, 54 as near ubiquitous and 50 as ubiquitous. The complexity of cellular microRNA expression estimates recapitulates tissue expression patterns and informs on the miRNA composition of plasma. ConclusionsThis study represents the most complete reference, to date, of miRNA expression patterns by primary cell type. The data is available through the human cellular microRNAome track at the UCSC Genome Browser (https://genome.ucsc.edu/cgi-bin/hgHubConnect) and an R/Bioconductor package (https://bioconductor.org/packages/microRNAome/).

genomics↗

In vivo imaging of the kinetics of microglial self-renewal and maturation in the adult visual cortex

Microglia are the resident immune cells in the brain with the capacity to autonomously self-renew. Under basal conditions, microglial self-renewal appears to be slow and stochastic, although microglia have the ability to proliferate very rapidly following depletion or in response to injury. Because microglial self-renewal has largely been studied using static tools, the mechanisms and kinetics by which microglia renew and acquire mature characteristics in the adult brain are not well understood. Using chronic in vivo two-photon imaging in awake mice and PLX5622 (Colony stimulating factor 1 receptor (CSF1R) inhibitor) to deplete microglia, we set out to understand the dynamic self-organization and maturation of microglia following depletion in the visual cortex. We confirm that under basal conditions, cortical microglia show limited turnover and migration. Following depletion, however, microglial repopulation is remarkably rapid and is sustained by the dynamic division of the remaining microglia in a manner that is largely independent of signaling through the P2Y12 receptor. Mathematical modeling of microglial division demonstrates that the observed division rates can account for the rapid repopulation observed in vivo. Additionally, newly-born microglia resemble mature microglia, in terms of their morphology, dynamics and ability to respond to injury, within days of repopulation. Our work suggests that microglia rapidly self-renew locally, without the involvement of a special progenitor cell, and that newly born microglia do not recapitulate a slow developmental maturation but instead quickly take on mature roles in the nervous system. Graphical Abstract(a) Microglial dynamics during control condition. Cartoon depiction of the heterogenous microglia in the visual cortex equally spaced. (b) During the early stages of repopulation, microglia are irregularly spaced and sparse. (c) During the later stages of repopulation, the number of microglia and the spatial distribution return to baseline. (d-f) We then created and ran a mathematical model that sampled the number of microglia, (d) the persistent doublets, (e) the rapid divisions of microglia and (f) the secondary divisions of microglia during the peak of repopulation day 2-day 3. The mathematical model suggested that residual microglia can account for the rapid repopulation we observed in vivo. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/977553v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@e198cborg.highwire.dtl.DTLVardef@f6484aorg.highwire.dtl.DTLVardef@1041083org.highwire.dtl.DTLVardef@1d8499a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗