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.
Highlights
The brain is composed of an incredible array of diverse cell types, of which, glial cells account for approximately half of this mosaic (Fu et al, 2013; Herculano-Houzel, 2014)
To query region specific gene signatures from astrocytes, Aldh1l1-eGFP mice were used to Fluorescence activated cell sorting (FACS) isolate astrocytes from four brain regions for mRNASeq analysis (Figure 1F)
We found seven transcription factor motifs (RPM >5) that were significantly enriched in differentially expressed genes (DEGs) from all four brain regions (Figure 3A), and the top three most significantly enriched motifs were that of Nkx2-2, Maz and Nuclear Factor-I (NFI)-family members NFIA, NFIB, NFIX (Figures 3B–D)
Summary
The brain is composed of an incredible array of diverse cell types, of which, glial cells account for approximately half of this mosaic (Fu et al, 2013; Herculano-Houzel, 2014). Astrocytes, a principal subtype of glial cell, were traditionally thought to be a homogenous population of cells that only function to provide support to neurons. Astrocytes are known to contribute to nearly every aspect of brain physiology and function (Khakh and Deneen, 2019). Their ability to execute a wide array of functions challenges the notion that astrocytes are a homogenous population of cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
