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Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus [RNA-Seq hippocampus]

ABSTRACT: Iron transporters are essential for maintaining cellular iron homeostasis. Among them, SLC22A17 mediates lipocalin-2 (LCN-2)-dependent iron transport, but its precise role in the brain remains unclear. Here, we show that Slc22a17 is critical for postnatal neurogenesis by regulating hippocampal iron balance. Conditional knockout of Slc22a17 in the murine brain causes early postnatal lethality, growth retardation, neural stem cell apoptosis, and cognitive deficits, largely due to oxidative stress from iron overload. Mechanistically, Slc22a17 interacts with p62 to modulate Nrf2 activity. Its loss aberrantly activates the Nrf2/HO-1 pathway, disrupting iron efflux and promoting accumulation of reactive oxygen species (ROS). These findings establish Slc22a17 as a key regulator of neuronal development and a potential therapeutic target for neurological disorders linked to iron dysregulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE306966 | GEO | 2025/09/08

REPOSITORIES: GEO

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Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus [ATAC-Seq]

Project description:Iron transporters are essential for maintaining cellular iron homeostasis. Among them, SLC22A17 mediates lipocalin-2 (LCN-2)-dependent iron transport, but its precise role in the brain remains unclear. Here, we show that Slc22a17 is critical for postnatal neurogenesis by regulating hippocampal iron balance. Conditional knockout of Slc22a17 in the murine brain causes early postnatal lethality, growth retardation, neural stem cell apoptosis, and cognitive deficits, largely due to oxidative stress from iron overload. Mechanistically, Slc22a17 interacts with p62 to modulate Nrf2 activity. Its loss aberrantly activates the Nrf2/HO-1 pathway, disrupting iron efflux and promoting accumulation of reactive oxygen species (ROS). These findings establish Slc22a17 as a key regulator of neuronal development and a potential therapeutic target for neurological disorders linked to iron dysregulation.

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Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus [RNA-Seq neurosphere]

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