Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain

Frontiers in Neuroscience
Brittney LozziBenjamin Deneen

Abstract

Astrocytes are the most abundant type of glial cell in the central nervous system and perform a myriad of vital functions, however, the nature of their diversity remains a longstanding question in neuroscience. Using transcription factor motif discovery analysis on region-specific gene signatures from astrocytes we uncovered universal and region-specific transcription factor expression profiles. This analysis revealed that motifs for Nuclear Factor-I (NFI) are present in genes enriched in astrocytes from all regions, with NFIB and NFIX exhibiting pan-astrocyte expression in the olfactory bulb, hippocampus, cortex, and brainstem. Further analysis into region-specific motif patterns, identified Nkx3-1, Stat4, Pgr, and Nkx6-1 as prospective region-specific transcription factors. Validation studies revealed that Nkx6-1 is exclusively expressed in astrocytes in the brainstem and associates with the promoters of several brainstem specific target genes. These studies illustrate the presence of multiple transcriptional layers in astrocytes across diverse brain regions and provide a new entry point for examining how astrocyte diversity is specified and maintained.

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Citations

Feb 5, 2021·Cells·Sun-Nyoung HwangHyosang Lee
Mar 12, 2021·Glia·Mira T KronschlägerJürgen Sandkühler
May 1, 2021·International Journal of Molecular Sciences·Debosmita SardarBenjamin Deneen
May 4, 2021·Biological Psychiatry·Ryan W LoganMarianne L Seney
Jul 15, 2021·Journal of Neuroscience Research·Christopher G Hart, Soheila Karimi-Abdolrezaee
Aug 13, 2021·Frontiers in Cellular Neuroscience·Aaron J MoulsonPeggy Assinck
Nov 10, 2021·Food & Function·Aurélie de Rus JacquetJean-Christophe Rochet

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Datasets Mentioned

BETA
GSE143282

Methods Mentioned

BETA
FACS
RNA-Seq
Assay
Immunoprecipitation
ChIP
PCR
PCA
ChIP-PCR

Software Mentioned

BaseSpace
ComplexHeatmap
fastQC
ggplot2
DESeq2
FACSDIVA
MultiQC
annotatePeaks
GenomicFeatures
ZEN2

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