The regenerative potential of adult Nestin+ cerebellar astroglia is limited compared to in neonates

2025 · doi:10.64898/2025.12.01.691510
preprint OA: closed CC-BY-ND-4.0
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The study investigated whether nestin (Nes)-expressing cerebellar progenitors in adult mice can regenerate after injury, comparing them to neonatal regenerative capacity. Using reporter mouse lines and genetic inducible fate mapping, the authors found that in adults Nes+ cells are mainly Bergmann glia (Nes+ Bg) with in vitro sphere-forming ability, and that after injury Nes+ Bg numbers rise via increased Nes expression in Hopx-expressing Bg, but neuroregeneration remains limited. ATAC-seq showed that adult Nes+ Bg differ from neonatal NEPs by silencing developmental genes, which the authors link to reduced regenerative ability, and sonic hedgehog signaling increased Nes+ Bg numbers after injury without restoring neurogenesis. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

There is a crucial need for strategies that stimulate repair in the adult brain. The neonatal mouse cerebellum can regenerate via the adaptive reprogramming of nestin (Nes)-expressing progenitors (NEPs). However, analysis of Nes + cells of the adult cerebellum is limited. Using reporter lines and genetic inducible fate mapping, we show that adult Nes + cells are mainly Bergmann glia ( Nes + Bg) that have in vitro sphere-forming ability. Following injury, Nes + Bg increase in number due to upregulation of Nes in Hopx -expressing Bg, but the cells exhibit limited regeneration. ATAC-seq of Nes + Bg reveals that silencing of developmental genes compared to neonatal NEPs contributes to the impaired regeneration. Activating sonic hedgehog signalling augments the number of Nes + Bg after injury but not neurogenesis, showing additional cues are required. Our results demonstrate an age-dependent decline in the regenerative potential of NEPs and highlight Nes+ Bg as potential injury-responsive cells that could facilitate regeneration.
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Abstract There is a crucial need for strategies that stimulate repair in the adult brain. The neonatal mouse cerebellum can regenerate via the adaptive reprogramming of nestin (Nes)-expressing progenitors (NEPs). However, analysis of Nes+ cells of the adult cerebellum is limited. Using reporter lines and genetic inducible fate mapping, we show that adult Nes+ cells are mainly Bergmann glia (Nes+ Bg) that have in vitro sphere-forming ability. Following injury, Nes+ Bg increase in number due to upregulation of Nes in Hopx-expressing Bg, but the cells exhibit limited regeneration. ATAC-seq of Nes+ Bg reveals that silencing of developmental genes compared to neonatal NEPs contributes to the impaired regeneration. Activating sonic hedgehog signalling augments the number of Nes+ Bg after injury but not neurogenesis, showing additional cues are required. Our results demonstrate an age-dependent decline in the regenerative potential of NEPs and highlight Nes+ Bg as potential injury-responsive cells that could facilitate regeneration. Competing Interest Statement The authors have declared no competing interest.

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