Speaker
Description
Understanding astrocyte heterogeneity is crucial for gaining insights into the development and function of the central nervous system. While the main types of cerebellar astrocytes can be identified based on their morphology and location, it remains unclear whether this classification reflects the full extent of cerebellar astrocyte heterogeneity. Furthermore, our overall
knowledge on their molecular profile, development, and functions is very limited. We recently provided the first evidence that an ontogenetic program, tightly regulated in space and time, generates the main types of cerebellar astrocytes from embryonic and postnatal progenitors with distinct fate potencies. However, the molecular profiles of these progenitor pools and the mechanisms governing the ontogenesis of different astrocyte types remain to be elucidated.
Through single-cell RNA sequencing and spatial transcriptomics in both postnatal and adult mouse cerebella, we unveiled the transcriptome of established astrocyte types and identified novel subtypes. Moreover, by developing a multimodal computational approach, we were able to reconstruct their maturation trajectories from postnatal progenitors. This analysis highlighted previously unrecognized progenitor sources for some astrocyte types and uncovered the gene expression cascades along distinct trajectories. Intriguingly, we shed new light on the ontogenesis and physiology of cerebellar nuclei astrocytes (CNA), which had previously received limited attention. Our transcriptomics data, complemented by clonal analyses, suggest that CNA arise from a distinct embryonic lineage compared to other astrocytes, and share a common origin with oligodendrocytes. Hence, the developing cerebellum appears to include two astrocyte lineages, clearly segregated at birth. Yet, they eventually converge into mature astrocyte profiles that despite spatial segregation show in some cases a high degree of transcriptional overlap, particularly in genes associated with homeostatic functions. This suggests that environmental cues play a crucial role in shaping cerebellar astrocyte heterogeneity, driving astrocytes of different embryonic origins toward shared homeostatic roles.
| Author(s) | V. Cerrato1*, G. Turrini1, I. Vitali2, B. Xiong2, L. Solanelles-Farré2, A. Lopes2, E. Magrinelli2, R. Bocchi3, J. Fischer-Sternjak4, M. Götz4, A. Buffo1, L. Telley2 |
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| Affiliation(s) | "1 University of Turin, Neuroscience Institute Cavalieri Ottolenghi (NICO), Torino, Italy, 2 University of Lausanne, Department of Fundamental Neuroscience, Lausanne, Switzerland, 3 University Of Geneva, Department Of Basic Neuroscience, Geneva, Switzerland, 4 Helmholtz Zentrum München, Munich, Germany" |
