Dual lineage origins contribute to neocortical astrocyte diversity
Abstract Astrocytes are not a uniform population but exhibit diverse morphological, molecular, and functional characteristics. However, how this diversity originates and becomes establishes during development, remains largely unknown. Here, using single-cell RNA sequencing and spatial transcriptomic...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61829-4 |
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| author | Jiafeng Zhou Ilaria Vitali Sergi Roig-Puiggros Awais Javed Iva Cantando Matteo Puglisi Paola Bezzi Denis Jabaudon Christian Mayer Riccardo Bocchi |
| author_facet | Jiafeng Zhou Ilaria Vitali Sergi Roig-Puiggros Awais Javed Iva Cantando Matteo Puglisi Paola Bezzi Denis Jabaudon Christian Mayer Riccardo Bocchi |
| author_sort | Jiafeng Zhou |
| collection | DOAJ |
| description | Abstract Astrocytes are not a uniform population but exhibit diverse morphological, molecular, and functional characteristics. However, how this diversity originates and becomes establishes during development, remains largely unknown. Here, using single-cell RNA sequencing and spatial transcriptomics, we identify five astrocyte subtypes with unique molecular features, spatial distributions and functions in the mouse neocortex and characterize essential regulators for their formation. Using TrackerSeq to trace clonally related astrocytes, we identify two distinct lineages that give rise to these five subtypes. One lineage derives from Emx1 + radial glial cells that initially generate neurons and later switch to astrocyte production. The other, with minimal neuronal output, predominantly produces a distinct subset of astrocytes marked by Olig2. Olig2 knockout disrupts lineage specification, leading to changes at molecular, morphological and functional levels. These findings shed light on the cellular mechanisms underlying astrocyte diversity, highlighting the presence of multiple radial glial cell subtypes responsible for generating cortical astrocyte subtypes. |
| format | Article |
| id | doaj-art-da81656fe4b64dd98be19ff15d63f5a7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da81656fe4b64dd98be19ff15d63f5a72025-08-20T03:43:12ZengNature PortfolioNature Communications2041-17232025-07-0116111710.1038/s41467-025-61829-4Dual lineage origins contribute to neocortical astrocyte diversityJiafeng Zhou0Ilaria Vitali1Sergi Roig-Puiggros2Awais Javed3Iva Cantando4Matteo Puglisi5Paola Bezzi6Denis Jabaudon7Christian Mayer8Riccardo Bocchi9Department of Basic Neurosciences, University of GenevaMax Planck Institute for Biological IntelligenceDepartment of Basic Neurosciences, University of GenevaDepartment of Basic Neurosciences, University of GenevaDepartment of Fundamental Neurosciences, University of LausanneDivision of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität MünchenDepartment of Fundamental Neurosciences, University of LausanneDepartment of Basic Neurosciences, University of GenevaMax Planck Institute for Biological IntelligenceDepartment of Basic Neurosciences, University of GenevaAbstract Astrocytes are not a uniform population but exhibit diverse morphological, molecular, and functional characteristics. However, how this diversity originates and becomes establishes during development, remains largely unknown. Here, using single-cell RNA sequencing and spatial transcriptomics, we identify five astrocyte subtypes with unique molecular features, spatial distributions and functions in the mouse neocortex and characterize essential regulators for their formation. Using TrackerSeq to trace clonally related astrocytes, we identify two distinct lineages that give rise to these five subtypes. One lineage derives from Emx1 + radial glial cells that initially generate neurons and later switch to astrocyte production. The other, with minimal neuronal output, predominantly produces a distinct subset of astrocytes marked by Olig2. Olig2 knockout disrupts lineage specification, leading to changes at molecular, morphological and functional levels. These findings shed light on the cellular mechanisms underlying astrocyte diversity, highlighting the presence of multiple radial glial cell subtypes responsible for generating cortical astrocyte subtypes.https://doi.org/10.1038/s41467-025-61829-4 |
| spellingShingle | Jiafeng Zhou Ilaria Vitali Sergi Roig-Puiggros Awais Javed Iva Cantando Matteo Puglisi Paola Bezzi Denis Jabaudon Christian Mayer Riccardo Bocchi Dual lineage origins contribute to neocortical astrocyte diversity Nature Communications |
| title | Dual lineage origins contribute to neocortical astrocyte diversity |
| title_full | Dual lineage origins contribute to neocortical astrocyte diversity |
| title_fullStr | Dual lineage origins contribute to neocortical astrocyte diversity |
| title_full_unstemmed | Dual lineage origins contribute to neocortical astrocyte diversity |
| title_short | Dual lineage origins contribute to neocortical astrocyte diversity |
| title_sort | dual lineage origins contribute to neocortical astrocyte diversity |
| url | https://doi.org/10.1038/s41467-025-61829-4 |
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