Biology subjects

Casares-Crespo, L.

Publications and source records attributed to Casares-Crespo, L..

2 recordsLinked to original sources

bioRxiv2025

Cell surface markers identify astrocyte subpopulations in the adult hippocampus with a heterogeneous response to aging

Astrocyte diversity is currently expanding both between and within specific brain regions. Here, we assessed the spatial distribution and transcriptomic profile of two hippocampal astrocyte subpopulations, defined by combinatorial expression of the cell surface astrocyte markers ACSA-1 or GLAST/SLC1A3, and ACSA-2 or ATP1B2. Fluorescence activated cell sorting and genome-wide transcriptomics by bulk RNAseq uncovered distinct transcriptional signatures of the two astrocyte subsets and highlighted heterogeneous responses during aging. The most abundant ATP1B2/GLAST double-positive astrocytes corresponded to mature glial cells with increased protein glycosylation and stable gene expression patterns. Signatures related to mitochondrial respiration and cholesterol metabolism were induced during aging in ATP1B2 single-positive astrocytes, while cell adhesion genes from the {gamma}-protocadherin cluster were repressed in double-positive astrocytes. Heterochronic co-culture assays with primary neurons show the loss of synaptogenic function of old ATP1B2/GLAST astrocytes. Our results complement previous studies demonstrating the presence of morphological and molecular astrocyte heterogeneity within the hippocampus, and uncover differences among astrocyte subsets in their transcriptomic response to aging.

neuroscience↗

bioRxiv2023

Autophagy is a cell-intrinsic driver of neural stem cell quiescence in hippocampal dentate gyrus development

Neurogenesis in the adult mammalian brain relies on the lifelong persistence of quiescent neural stem cell (NSC) reservoirs. Little is known about the mechanisms that lead to the initial establishment of NSC quiescence during development. Here, we show that protein aggregates and autophagy machinery components accumulate in quiescent NSCs and that pharmacological blockade of autophagy disrupts quiescence. Conversely, increasing autophagy through AMPK/ULK1 activation instructs the acquisition of the quiescent state. Selective ablation of Atg7, a critical gene for autophagosome formation, in hippocampal radial-glia like NSCs at early and late postnatal stages compromises the initial acquisition and maintenance of quiescence during the formation of the dentate gyrus SGZ niche. Therefore, we demonstrate that autophagy is cell-intrinsically required to establish radial glia-like NSC quiescence during hippocampal development. Our results uncover a fundamental role of autophagy in the transition of developmental NSCs into their dormant adult form, paving the way for studies directed at further understanding the mechanisms of stem cell niche formation and maintenance in the mammalian brain.

neuroscience↗