The Diversified Astrocyte Developmental Programs are Modulated by Primary Ciliary Signaling

This SuperSeries is composed of the SubSeries listed below. Astrocyte diversity is greatly influenced by local environmental modulation. In this study, we analyzed how primary ciliary signaling modulates astrocyte subtype-specific maturation and accessed the impact of ciliary deficient astrocytes on neuronal programs and behaviours. Comparative single-cell transcriptomics revealed that primary cilia mediate canonical Shh signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy, and metabolism. Independent of canonical Shh signaling, primary cilia are important regulators for astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics revealed that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain