The origin of astrocytes revealed
A study by Faculty of Medicine and its Synapsy Centre reveals that the diversity of astrocytes in the cortex originates from two distinct types of progenitors. This discovery redefines the essential role of astrocytes in the central nervous system and opens up new therapeutic possibilities.
© R. Bocchi. The astrocytes of the cortex are not a homogeneous population.
Astrocytes, once considered a homogeneous population of brain cells with a passive support role, are now recognised as key players in the central nervous system. They form the blood-brain barrier, support neuronal metabolism and regulate synaptic connectivity. This wide range of functions, combined with their emerging role in many psychiatric and neurodegenerative disorders, suggests that astrocytes may not form a homogeneous population, but are in fact composed of different cell subtypes.
This has been demonstrated by the team led by Riccardo Bocchi, Ambizione researcher at the Faculty of Medicine (FacMed) of the 玉美人传媒 (UNIGE), using high-resolution single-cell sequencing. ‘We have identified five distinct subtypes of astrocytes in the mouse cortex, each occupying different specific cortical regions,’ he explains. But for the researcher and his team, a key question remained unanswered despite this discovery: how does astrocyte diversity arise during development? This is the subject of their new study, published in .
Two types of progenitors
Riccardo Bocchi explains: ‘Until now, it was thought that all cortical astrocytes originated from Emx1+ progenitors, cells that sequentially produce neurons during embryogenesis and then astrocytes towards birth.’ His study shows that this is indeed the case, but only for part of the astrocyte population. A second lineage of astrocytes expressing the transcription factor Olig2 comes from another type of progenitor.
And this difference in origin has a functional impact. Astrocytes from this second lineage are mainly involved in the formation of new synapses, a process that is fundamental to the construction of healthy neural circuits. ‘When we deactivated Olig2 in mice,’ explains Riccardo Bocchi, ‘we not only observed a reduction in this subpopulation of astrocytes, but also a significant decrease in the number of synapses, highlighting their crucial role in synaptogenesis.’
Therapeutic implications
This discovery has important potential therapeutic implications, particularly for cell reprogramming approaches aimed at converting astrocytes into neurons to replace neurons lost after brain damage, typically after a stroke. Indeed, selecting astrocytes that share a developmental lineage with neurons, such as those of the Emx1鈦� lineage, could improve the effectiveness of the approach. Conversely, therapeutic manipulation of the Olig2 lineage could help restore the loss of synapses observed in many psychiatric disorders.
This study provides a model for rethinking how we classify and manipulate astrocytes in the brain. As Riccardo Bocchi concludes, ‘understanding the diversity of astrocytes is a crucial step towards tailored interventions to combat brain disorders.’
31 Jul 2025