An Astrocyte Transplantation Method to Investigate Astrocyte Development and Diversity in the Central Nervous System...

Astrocytes have rich structural, molecular, and physiological properties and show remarkable diversity in form and function that supports circuit-specific physiology within the central nervous system (CNS). However, the developmental mechanisms and cellular interactions that help to locally and globally diversify astrocytes with the CNS remain to be better understood. Understanding these processes will help to understand how astrocytes establish specialized microenvironments in the healthy brain and how they may differentially respond to CNS injury and disease. Here, we describe a cell transplantation method that enables the study of cell-autonomous and non-cell-autonomous determinants of astrocyte diversification by tracking the developmental trajectory of astrocytes transferred to the same or different regions of the mouse brain. With this method, it is possible to evaluate how astrocytes mature in "familiar" or "foreign" environmental contexts, for example, by transplanting cortical astrocytes into the cortex (a familiar context) or cerebellum (a foreign context). Also, with this method, the effect of developmental state on the ability of transplanted astrocytes to integrate into the brain environment can be studied, for example, by transplanting embryonically or postnatally derived cortical astrocytes into the cerebellum and monitoring their maturation within the recipient brain. We find that this transplantation method provides a flexible and robust approach to investigate how intrinsic cell properties and extrinsic cues from the extracellular environment shape astrocyte diversity.