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Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression

The generation of a correctly sized cerebral cortex with all-embracing neuronal and glial cell–type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb repressive complex 2 (PRC2...

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Detalles Bibliográficos
Autores principales: Amberg, Nicole, Pauler, Florian M., Streicher, Carmen, Hippenmeyer, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629739/
https://www.ncbi.nlm.nih.gov/pubmed/36322669
http://dx.doi.org/10.1126/sciadv.abq1263
Descripción
Sumario:The generation of a correctly sized cerebral cortex with all-embracing neuronal and glial cell–type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb repressive complex 2 (PRC2), and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here, we use mosaic analysis with double markers (MADM)–based single-cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context, our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior.