Cell by cell: molecular approaches to understanding astrocyte heterogeneity in the CNS
Astrocytes are one of the major cell types in the mammalian brain. They perform many important functions, including potassium homeostasis, neurotransmitter uptake, synapse formation and maintenance, as well as regulation of the blood brain barrier (BBB). Given their critical role in normal brain function, it is unsurprising that all CNS pathologies show astrocyte involvement. Hence, understanding astrocyte function is critical if we are to understand the brain - and how to repair it after injury or disease.
Astrocytes have traditionally been studied as a homogeneous set of cells. However, recent reports suggest that this is wrong and that astrocytes are in fact a highly heterogeneous cell population, showing considerable variation in morphology, gene expression and physiology. This raises the question of whether astrocytes are actually specialised to perform specific functions in defined regions of the CNS. Furthermore, it is also unclear how heterogeneity impacts on injury and neurodegenerative disease – and whether this explains regional predisposition to conditions such as astrocytoma.
We are seeking to explain astrocyte heterogeneity and its functional role in the CNS using a number of complementary approaches. Using single cell transcriptomic methods, my lab has recently identified eight distinct astrocyte subtypes in the adult mouse brain. Adopting a bottom up approach, we are now using unique genetic tools and in vivo 2-photon Ca2+ imaging to understand the role of these specific astrocyte subtypes in creating functional heterogeneity in the CNS.
Matthew Holt, Laboratory for Glia Biology, VIB Center for Brain & Disease Research, KU Department of Neuroscience, Leuven, Belgium.