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Astroglial Ezh2 regulates early astrocyte morphogenesis and affects the coverage of astrocyte endfeet on blood vessels

ABSTRACT: Astroglial Ezh2 regulates early astrocyte morphogenesis and affects the coverage of astrocyte endfeet on blood vessels

PROVIDER: PRJNA1194629 | ENA |

REPOSITORIES: ENA

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Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

Project description:Astrocytes are intimately linked with brain blood vessels, a relationship critical for neuronal function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. By characterizing structural and transcriptional changes in mouse cortical astrocytes during the first two postnatal weeks, we find that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, is highly expressed in astrocytes at birth and then decreases rapidly. Astrocyte-selective ablation of Hmgb1 at birth affects astrocyte morphology and endfoot placement, alters distribution of endfoot proteins connexin43 and aquaporin-4, induces transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupts endothelial ultrastructure. While lack of astroglial Hmgb1 does not affect the blood-brain barrier or angiogenesis postnatally, it impairs neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as a key player in postnatal gliovascular maturation.

2023-07-10 | GSE236429 | GEO

Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

Project description:Astrocytes are intimately linked with brain vessels, a relationship that is critical for neuronal health and function. However, key astroglial molecular factors that drive these physical and functional associations during postnatal brain development have not yet been identified. We characterized structural and transcriptional changes in mouse cortical astrocytes and microvessels during the first two postnatal weeks and found that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, was highly expressed in astrocytes at birth to then decreased rapidly. Astrocyte-selective ablation of Hmgb1 in newborn mice affected astrocyte morphology and endfoot placement, induced disruption of endfoot proteins connexin43 and aquaporin-4, induced transcriptional changes in astrocytes, and profoundly altered endothelial cell ultrastructure. While lack of astroglial Hmgb1 did not affect the blood-brain barrier or angiogenesis postnatally, it impaired neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as a key player in postnatal gliovascular maturation.

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Project description:Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

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Proteomic analysis for astroglial exosomes

Project description:LC/MS/MS analysis was performed on astroglial exosome samples (3 biological replicates) to identify proteins expressed on the surface of astroglial exosomes. Thes astroglial exosome samples were purified using size-exclusion column from astrocyte conditioned medium (ACM) of primary astrocyte cultures.

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Astroglial Ezh2 regulates early astrocyte morphogenesis and affects the coverage of astrocyte endfeet on blood vessels

Project description:To further investigate how Ezh2 derived from cortical astrocytes regulates cell morphology, RNA-seq analysis was performed to examine transcriptomic changes in cortical astrocytes isolated from Ezh2 conditional knockout mice and wild-type littermates at P5. Approximately 4,900 transcripts exhibited differential expression between Ezh2fl/fl and Ezh2-cKO-Aldh1l1 mouse cortical astrocytes, with a fold change ≥2 and a p-value <0.05. After further screening of the highly expressed gene subset among the differentially expressed genes, we found that the upregulated genes were enriched in processes related to gliogenesis, cell differentiation, and cytoskeletal organization. These findings highlight the critical role of astrocytic Ezh2 in the morphological development of astrocytes.

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2017-01-27 | GSE72937 | GEO

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