Astrocytes, known for their crucial role in supporting neurons and maintaining brain health, have been predominantly studied in gray matter (GM), which is involved in information processing. However, white matter astrocytes, which support long-range neural connections, remain poorly understood. This study fills a major knowledge gap by showing that WM astrocytes are not a uniform population but consist of distinct subtypes with specialized roles. The team was led by Dr. Judith Fischer-Sternjak from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) München, alongside Prof. Magdalena Götz from Helmholtz Munich, LMU and the Munich Cluster for Systems Neurology (SyNergy).

“Our findings challenge the traditional view that white matter astrocytes are a homogeneous population,” says Judith Fischer-Sternjak. “Instead, we see clear evidence of specialized subtypes, including one with significant proliferative capacity, which could be harnessed for brain repair.”

“As we have shown previously that proliferating astrocytes can be harnessed for repair, we are very excited to find these even in the WM of healthy brains,” adds Magdalena Götz.

A Potential Brain Repair Reservoir

The study identified two distinct types of cortical white matter astrocytes. One is more widely distributed throughout the brain and has been evolutionarily conserved, probably being involved in supporting nerve fibers, facilitating cell communication, and regulating metabolism. The other is a highly specialized subtype found primarily in the cortical white matter. This subtype has a remarkable ability to proliferate and is influenced by specific pathways involving interactions with other brain cells.

Notably, the researchers discovered that some of these proliferating astrocytes can migrate from the white matter into the gray matter. This suggests that certain white matter regions may serve as a hidden reservoir for generating new astrocytes, potentially contributing to brain maintenance.

Isolation of single cells from cortical GM, WM and the SEZ

a, Schematic representation of the workflow used to dissect all three regions from 2–3-month-old C57BL/6J mice to generate the single-cell suspension for scRNA-seq. b, t-distributed stochastic neighbor embedding (t-SNE) visualization of scRNA-seq data from the three regions, with cells color-coded based on their cell types. c, t-SNE visualization showing expression levels (normalized) of common markers for astrocytes. d, Gene expression profiles obtained from scRNA-seq data, segregated according to the cell types identified in b and representing genes used to calculate the astrocyte score. e, Cell type scores used to annotate the scRNA-seq dataset in b.

Toward Therapeutic Applications

The discovery of proliferative astrocytes in the WM raises possibilities for regenerative medicine. By understanding the mechanisms that regulate astrocyte proliferation, researchers could develop new therapies for brain injuries and neurodegenerative diseases such as multiple sclerosis, where WM integrity is compromised.

“This study opens up exciting possibilities for regenerative medicine”, says Dr. Riccardo Bocchi, the first author of the study. “The discovery of proliferative astrocytes in the WM unveils exciting opportunities, particularly in conditions involving WM damage or degeneration.”

Source – Ludwig-Maximilians-Universität (LMU) München