Astrocyte Subtypes Perform Distinct Jobs in the Developing and Injured Brain

A study published in Nature by researchers at Baylor College of Medicine answers a long-standing question about astrocytes, the star-shaped cells that are the brain and spinal cord’s most abundant support cells: whether, like neurons, they split into specialized types that each handle different jobs. Using a newly developed genetic tool, the team found that they do. Distinct astrocyte subtypes help form connections between nerve cells, shape the brain circuits involved in learning and memory, and support recovery after a stroke. 

Astrocytes were already known to perform a wide range of jobs—helping neurons communicate, sustaining brain circuits, nourishing nerve cells, maintaining the blood-brain barrier, and responding to injury and disease—but whether specific jobs belonged to specific astrocyte subtypes, as is the case for neurons, had remained unclear, since earlier studies showing astrocytes vary molecularly didn’t establish whether those differences meant different roles in a living brain. 

To test that directly, the researchers focused on CD51, a surface protein present on some astrocytes but not others that earlier work had linked to molecularly distinct groups. Since no tools existed to isolate CD51-positive and CD51-negative astrocytes in a living brain, the team built a new mouse line to label and control each group separately, then compared them in the cerebral cortex and the hippocampus, across developing, adult and injured brains.

The two groups turned out to be distinct subtypes, each with its own shape, activity and developmental path. Co-first author Michael Williamson explained that the cortex showed a clear division of labor: “We discovered that CD51+ astrocytes have a specialized job: they help form synapses in the developing and injured cortex. CD51- astrocytes don’t do this. CD51+ astrocytes do this job using a protein called glypican 6.”

In the hippocampus, CD51-positive astrocytes similarly supported and adapted memory circuits while CD51-negative astrocytes did not, with the CD51 protein itself driving that circuit rewiring. The distinction held up under injury as well: in mice that had a stroke, only CD51-positive astrocytes helped restore brain function by remodeling connections between neurons.

According to corresponding author Benjamin Deneen, the findings reshape the basic picture of what astrocytes are: “Altogether, our findings change how we think about astrocytes. For a long time, astrocytes were considered largely uniform. We’ve shown that they include specialized subtypes with distinct jobs in the developing, adult and injured brain, much like what we see for neurons. Going forward, studies of astrocytes in health and disease will need to consider which subtypes are involved.”