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Scientists Find Markers for Unique Radial Glia That May Have led the Brain to Evolve

NEW YORK(GenomeWeb) — Using mRNA sequencing scientists from the University of California, San Francisco and Fluidigm have determined that outer radial glia (oRG) cells may be responsible for brain expansion during evolution.

oRG and another type of neural stem cell called ventricular radial glia (vRG) come from distinct areas of the brain — the ventricular zone and the outer subventricular zone. The vRG and oRG cells reside in distinct niches defined by differences in anatomical location, provision of growth factors, cell morphology, and behavior. While oRG cells represent the majority of radial glia, the molecular features sustaining the properties of oRG cells in the outer subventricular zone are largely unknown, and long-term proliferation capacity of these cells has not been examined.

In their work described in a paper published today in Cell, the researchers used a single-cell capture and mRNA sequencing approach in order to better understand the molecular programs specifically used by oRG cells. Alex Pollen, a graduate student in UCSF’s department of neurology and a co-author on the paper, told GenomeWeb that he and his colleagues collected tissue samples from the outer subventricular zone and the ventricular zone, but without additionally enriching the cells.

Single-cell RNA sequencing libraries were generated using Fluidigm's C1 single-cell auto prep integrated fluidic circuit, Clontech's Smarter ultra low RNA kit (Clontech), and Illumina's Nextera XT DNA sample preparation kit. The scientists then sorted out the radial glia cells in silicoto assign specific signatures to the two different radial glia cell types.

They aligned reads by using TopHat2, and quantified the expression of RefSeq genes by the featureCounts routine. Gene expression values were normalized based on library size as counts-per-million reads.

Scientists were then able to assign transcriptional signatures associated with expression in specific genes to both types of radial glia cells. While both cells share some similarities, oRG cells preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR. All of these operations seem necessary to develop and expand the human neocortex, a process that is not yet well understood, and indicates that these cells may hold the key to understanding how the primate brain evolved into the modern human one, the researchers said in the study. 

They also noted interesting similarities between oRG’s unique translocation process and that of glioblastoma cells. The same cells are enriched in both processes, so better understanding these oRG cells could lead to more insight into how these cancerous tumors develop, potentially resulting in improved treatments, they said.