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Single-cell RNA-seq reveals neural progenitor subpopulations and divergent astrocyte lineages

ABSTRACT: Single-cell RNA-seq reveals neural progenitor subpopulations and divergent astrocyte lineages

PROVIDER: PRJNA529460 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8797104.fastq.gz	Fastqsanger.gz
	SRR8797105.fastq.gz	Fastqsanger.gz
	SRR8797106.fastq.gz	Fastqsanger.gz
	SRR8797107.fastq.gz	Fastqsanger.gz

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Single-cell RNA-seq reveals neural progenitor subpopulations and divergent astrocyte lineages

Project description:Astrocytes are one of the most abundant cell types in the mammalian central nervous system. Their diversity was widely investigated in the adult brain recently. However, the heterogeneity of astrocyte progenitors in their early developmental stage is still not clear. In this study, we dissected the subpopulations of neural progenitor cells at the neurogenesis and the early gliogenesis stages by single-cell RNA sequencing analysis. Interestingly, we identified two astrocyte progenitor subgroups from the cerebral cortex. The astrocyte subgroups highly express Sparc or Sparcl1, which were reported have contrary functions in astrocytes to regulate synapse formation. Further analysis for subpopulations of neural progenitors from the ventral forebrain also identified two astrocyte progenitor subgroups, showing similar gene expression patterns as in the cortex. Surprisingly, clustering analysis between the subpopulations from the dorsal and the ventral forebrains showed that the astrocyte progenitors expressing Sparc or Sparcl1 were clustered together, irrespective of their derived regions. These results showed an early divergence of astrocyte progenitors and their cross-regional conservation at the start of gliogenesis during brain development.

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CD51 expression delineates functionally distinct astrocyte subpopulations in neural circuits

Project description:Astrocytes execute a diverse range of tasks that facilitate brain physiology, raising the possibility that these diverse astrocytic roles are enabled by functionally distinct subtypes1,2. Recent studies identified molecular diversity amongst astrocytes3, however whether this molecular heterogeneity reflects specialized astrocyte subpopulations with distinct functions remains unknown. Leveraging prior molecular and functional studies4, we generated a CD51-FLP mouse line that enables the direct comparison of functional properties between CD51+ and CD51- astrocyte subpopulations in neural circuits in vivo. Here we show that CD51+ and CD51- astrocytes are endowed with unique morphological, physiological, and developmental properties in both the cortex and hippocampus. Functional studies demonstrate that CD51+ astrocytes selectively promote synapse formation in the developing cortex and circuit plasticity in the hippocampus. Mechanistically, we found that CD51+ astrocytes function through glypican 6 to promote synapse formation in the cortex, while CD51 itself drives circuit plasticity in the hippocampus. Applying these findings to brain injury, we found that exploiting the unique properties of CD51+ astrocytes promotes functional recovery after stroke through enhanced synaptic remodeling. Taken together, our studies identify specialized astrocyte subpopulations that exhibit distinct functional properties in the developing, mature, and injured brain.

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CD51 expression delineates functionally distinct astrocyte subpopulations in neural circuits

Project description:CD51 expression delineates functionally distinct astrocyte subpopulations in neural circuits

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Divergent transcriptional regulation of astrocyte reactivity across disorders

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Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_LPS]

Project description:Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_LPS]

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Divergent transcriptional regulation of astrocyte reactivity across disorders [RNA-seq]

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Project description:Astrocytes differentiate into a spectrum of neurotoxic and neuroprotective reactive subpopulations after CNS injury and in disease. In astrocyte conditional ADCY10 (sAC) knockout mice, reactive astrocytes exhibit a shift towards neurotoxic phenotypes implicating sAC as a critical regulator of neuroprotective astrocyte differentiation.

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