Monitoring regional astrocyte diversity by cell-type specific proteomic labeling in vivo

Astrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region-specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an Aldh1l1- MetRSL274G mouse line that allows cell-type specific labeling of newly synthesized proteins in vivo and analyzed astrocytic proteins from four different brain regions by mass spectrometry. Identified proteins are specific for astrocytes and show a high overlap with proteins compiled in AstroProt, a newly established database for astrocytic proteins. Gene enrichment analysis reveals high overlap among brain regions, and only subtle changes in abundances of key astrocytic proteins for hippocampus, cortex and striatum. However, the cerebellar proteome stands out with proteins being associated with calcium signaling or bipolar disorder. Subregional differences of translation dynamics in single hippocampal astrocytes indicates distinct subregional heterogeneity and highlights the applicability of our toolbox to study dynamic astrocytic proteomes in vivo.