Towards the Transcriptionally based Classification of L6b in the Adult Mouse Brain

Early generated and largely transient cortical subplate neurons perform important developmental functions in all mammals. However, only a subset of this cell population survives into adulthood as layer 6b (L6b) in mouse and interstitial white matter cells in human. L6b is comprised of a diverse population of cells and various characteristics of mouse L6b cells have been investigated individually. Here, our aim is to combine transcriptomic clustering of cells based on single cell gene expression with more conventional data to arrive at a unified cell taxonomy via a comprehensive meta-analysis. However, matching up various anatomical and physiological parameters with the classification based on single cell transcriptomic datasets is complex. Here we explore the origins of these difficulties. Our analysis revealed glutamatergic L6b class Slc17a8 (317), which stands out due to its unique gene expression, global localization, and expression of orexin/hypocretin receptor 2 (Hcrtr2). We outline the need of future studies to employ multiple approaches to generate congruent clustering. We propose that the weight of each dimension must be revaluated, with transcriptomic data requiring semi-independent clustering.