Astrocytes play a crucial role in supporting neurons and maintaining brain health. To date, however, their heterogeneity has been studied primarily in gray matter (GM), which is responsible for information processing. In contrast, white matter astrocytes, which support long-range neuronal connections, have been little studied. This study closes a key knowledge gap by showing that WM astrocytes are not a homogeneous cell population but consist of different subtypes with specialized functions. The work was led by Dr. Judith Fischer-Sternjak from Helmholtz Munich and LMU and Professor Magdalena Götz from Helmholtz Munich, LMU and the SyNergy Cluster of Excellence.
"Our results refute the previous assumption that white matter astrocytes form a uniform cell group," explains Judith Fischer-Sternjak. "Instead, we found clear evidence of specialized subtypes, including a cell type with considerable proliferative potential that could be used for brain repair."
"As we have already been able to prove that proliferating astrocytes can contribute to regeneration, we are particularly excited to now also discover them in the white matter of healthy brains," adds Magdalena Götz.
A hidden reservoir for brain regeneration
The study identified two different types of astrocytes in the cortical white matter. One of these types is widely distributed in the brain, evolutionarily conserved and presumably involved in supporting nerve fibers, cell communication and metabolic regulation. The other is a highly specialized subtype found primarily in the cortical white matter. This cell type is characterized by a remarkable ability to proliferate and is influenced by specific signaling pathways that interact with other brain cells.
Remarkably, the researchers found that some of these proliferating astrocytes can migrate from the white matter into the gray matter. This suggests that certain regions of the white matter could serve as a hidden reservoir for the formation of new astrocytes and thus contribute to the long-term preservation of brain function.
New perspectives for therapeutic applications
The discovery of proliferating astrocytes in white matter opens up promising possibilities for regenerative medicine. A better understanding of the mechanisms that control astrocyte proliferation could lead to the development of new therapies for brain injuries and neurodegenerative diseases such as multiple sclerosis, in which the integrity of white matter is compromised.
"This study opens up exciting perspectives for regenerative medicine," says Dr. Riccardo Bocchi, first author of the study. "The discovery of proliferating astrocytes in white matter creates new therapeutic approaches, especially for diseases associated with white matter damage or degeneration."
Riccardo Bocchi, Manja Thorwirth, Tatiana Simon-Ebert et al.: Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter. Nature Neuroscience, 2025