Astrocyte maturation creates a stage-specific niche that instructs hippocampal neurogenesis.
5 affiliations
- 1Department of Neurosurgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
- 2Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
- 3Instituto de Biomedicina de Valencia (IBV), CSIC, València, Spain.
- 4Centro de Investigación Príncipe Felipe (CIPF)-Associated Unit to the Instituto de Biomedicina de Valencia (IBV), Valencia Biomedical Research Foundation, València, Spain.
- 5Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Abstract
Astrocytes are a major part of the hippocampal stem cell niche and have been shown to control several steps of neurogenesis, from neural stem and precursor cell (NSPC) proliferation to the differentiation and maturation of newborn neurons. With the aim to identify new factors by which astrocytes promote neurogenesis, we isolated hippocampal astrocytes across key postnatal stages (p3, p10, and p14) and collected astrocyte conditioned medium (ACM) while keeping them for 1 week in culture. Depending on the developmental stage of the astrocytes, we uncovered a shift in the astrocyte secretome. Specifically, ACM from p3 progenitor-like astrocytes promoted a gliogenic program when applied to adult hippocampal NSPCs, while ACM derived from p10 and p14 astrocytes exhibited potent neurogenic properties. To define the molecular basis underlying the acquisition of these neurogenic properties, we performed transcriptomic profiling of astrocytes directly isolated at p3, p10 and p14 as well as astrocytes isolated at these stages that were kept in culture for 7 days. These data sets were integrated with metabolomic analysis of astrocyte-conditioned media from p3 and p14 astrocytes revealing distinct stage-specific programs enriched for secretory and metabolic pathways. Notably, we identified a combination of metabolites that accumulates as astrocytes mature and act as potent drivers of neuronal differentiation. Our findings demonstrate that astrocyte maturation establishes a metabolically and transcriptionally defined, stage-specific niche that instructs NSPC fate and drives neurogenesis.
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BibTeX
@article{masouti2026astrocyte,
title = {{Astrocyte maturation creates a stage-specific niche that instructs hippocampal neurogenesis.}},
author = {Evangelia Masouti and Lucía Casares-Crespo and Andreas Sagner and Arne Gessner and Martin F Fromm and Helena Mira and Ruth Beckervordersandforth},
journal = {Frontiers in cellular neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fncel.2026.1966983},
url = {https://europepmc.org/article/MED/42908519},
note = {CC BY},
}
RIS
TY - JOUR
TI - Astrocyte maturation creates a stage-specific niche that instructs hippocampal neurogenesis.
AU - Evangelia Masouti
AU - Lucía Casares-Crespo
AU - Andreas Sagner
AU - Arne Gessner
AU - Martin F Fromm
AU - Helena Mira
AU - Ruth Beckervordersandforth
PY - 2026
DA - 2026/10/07
JO - Frontiers in cellular neuroscience
DO - 10.3389/fncel.2026.1966983
UR - https://europepmc.org/article/MED/42908519
AB - Astrocytes are a major part of the hippocampal stem cell niche and have been shown to control several steps of neurogenesis, from neural stem and precursor cell (NSPC) proliferation to the differentiation and maturation of newborn neurons. With the aim to identify new factors by which astrocytes promote neurogenesis, we isolated hippocampal astrocytes across key postnatal stages (p3, p10, and p14) and collected astrocyte conditioned medium (ACM) while keeping them for 1 week in culture. Depending on the developmental stage of the astrocytes, we uncovered a shift in the astrocyte secretome. Specifically, ACM from p3 progenitor-like astrocytes promoted a gliogenic program when applied to adult hippocampal NSPCs, while ACM derived from p10 and p14 astrocytes exhibited potent neurogenic properties. To define the molecular basis underlying the acquisition of these neurogenic properties, we performed transcriptomic profiling of astrocytes directly isolated at p3, p10 and p14 as well as astrocytes isolated at these stages that were kept in culture for 7 days. These data sets were integrated with metabolomic analysis of astrocyte-conditioned media from p3 and p14 astrocytes revealing distinct stage-specific programs enriched for secretory and metabolic pathways. Notably, we identified a combination of metabolites that accumulates as astrocytes mature and act as potent drivers of neuronal differentiation. Our findings demonstrate that astrocyte maturation establishes a metabolically and transcriptionally defined, stage-specific niche that instructs NSPC fate and drives neurogenesis.
SN - 1662-5102
ER -