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A research team 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), has identified different subtypes of white matter (WM) astrocytes, including a unique type with the ability to multiply and potentially aid in brain repair. Using single-cell RNA sequencing and spatial transcriptomics, the scientists mapped astrocyte diversity across different brain regions and species, providing the first detailed molecular profile of WM astrocytes.
Unveiling White Matter Astrocyte Diversity
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.
“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.
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.”
About the Researchers:
Dr. Judith Fischer-Sternjak, Deputy Director of the Institute of Stem Cell Research and Director of Operations Stem Cell Center at Helmholtz Munich, Contact: judith.fischer@helmholtz-munich.de
Prof. Magdalena Götz, Director of the Institute of Stem Cell Research at Helmholtz Munich, Professor and Chair of Physiological Genomics at the Biomedical Center of the LMU, and Board Member of the Munich Cluster of Systems Neurology (SyNergy), Contact: Magdalena.goetz@helmholtz-munich.de
Dr. Riccardo Bocchi, Principal Investigator at the Department of Basic Neuroscience, University of Geneva, Switzerland, Contact: Riccardo.Bocchi@unige.ch
About Helmholtz Munich:
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has around 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
Dr. Judith Fischer-Sternjak, Deputy Director of the Institute of Stem Cell Research and Director of Operations Stem Cell Center at Helmholtz Munich, Contact: judith.fischer@helmholtz-munich.de
Bocchi et al., 2025: Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter. Nature Neuroscience. DOI: 10.1038/s41593-025-01878-6
Proliferative astrocytes in the white matter of the murine brain.
Judith Fischer-Sternjak
©Judith Fischer-Sternjak
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