Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells

Adult mammalian brains generate new neurons throughout life in two main niches, the dentate gyrus of the hippocampus and the subventricular zone, starting from neural stem cells (NSCs). Adult hippocampal neurogenesis is crucial for learning and memory and decreases during aging. As defined in mouse...

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Main Authors: Laura Micheli, Maurizia Caruso, Giorgio D’Andrea, Daniel Volpe, Manuela Ceccarelli, Felice Tirone
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1605116/full
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author Laura Micheli
Maurizia Caruso
Giorgio D’Andrea
Daniel Volpe
Manuela Ceccarelli
Felice Tirone
author_facet Laura Micheli
Maurizia Caruso
Giorgio D’Andrea
Daniel Volpe
Manuela Ceccarelli
Felice Tirone
author_sort Laura Micheli
collection DOAJ
description Adult mammalian brains generate new neurons throughout life in two main niches, the dentate gyrus of the hippocampus and the subventricular zone, starting from neural stem cells (NSCs). Adult hippocampal neurogenesis is crucial for learning and memory and decreases during aging. As defined in mouse models, NSCs, which are prevalently quiescent, develop into proliferating progenitor cells, neuroblasts, and immature and mature neurons. Two visions for NSC self-renewal in the dentate gyrus have been proposed, one postulating persistent self-renewal, with cycles of rest and reactivation even in old age, and the other proposing a short-lived NSC model. Single-cell RNA sequencing and clonal studies, discussed in this review, have shed light on the developmental steps of neurogenic cells and the modality of self-renewal, revealing the presence in the adult dentate gyrus of NSC heterogeneous populations, one long-lived and another rapidly depleted at an early age. Another relevant question is whether adult neurogenesis occurs in humans. A few single-cell RNA-seq studies show that new neurons, with prolonged neuronal maturation, are continuously generated at low frequency from stem/progenitor cells, which results in the accumulation of immature granule cell neurons. This suggests an important role of these cells in human neurogenesis and hence interspecies differences in the neurogenic process dynamics. This review is focused on transcriptomic studies that have faced these and other NSC issues by analyzing developmental trajectories of neural cells and NSCs gene expression profiles in specific experimental settings of hippocampal neurogenesis, and also in mouse models with deletion or overexpression of specific genes to reproduce neural pathologies.
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spelling doaj-art-5c86c03bf9c94f5bb27e585d74f3dd5d2025-08-20T02:00:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.16051161605116Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cellsLaura Micheli0Maurizia Caruso1Giorgio D’Andrea2Daniel Volpe3Manuela Ceccarelli4Felice Tirone5Institute of Biochemistry and Cell Biology, National Research Council, Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, Rome, ItalyOnco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children’s Hospital IRCCS, Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, Rome, ItalyAdult mammalian brains generate new neurons throughout life in two main niches, the dentate gyrus of the hippocampus and the subventricular zone, starting from neural stem cells (NSCs). Adult hippocampal neurogenesis is crucial for learning and memory and decreases during aging. As defined in mouse models, NSCs, which are prevalently quiescent, develop into proliferating progenitor cells, neuroblasts, and immature and mature neurons. Two visions for NSC self-renewal in the dentate gyrus have been proposed, one postulating persistent self-renewal, with cycles of rest and reactivation even in old age, and the other proposing a short-lived NSC model. Single-cell RNA sequencing and clonal studies, discussed in this review, have shed light on the developmental steps of neurogenic cells and the modality of self-renewal, revealing the presence in the adult dentate gyrus of NSC heterogeneous populations, one long-lived and another rapidly depleted at an early age. Another relevant question is whether adult neurogenesis occurs in humans. A few single-cell RNA-seq studies show that new neurons, with prolonged neuronal maturation, are continuously generated at low frequency from stem/progenitor cells, which results in the accumulation of immature granule cell neurons. This suggests an important role of these cells in human neurogenesis and hence interspecies differences in the neurogenic process dynamics. This review is focused on transcriptomic studies that have faced these and other NSC issues by analyzing developmental trajectories of neural cells and NSCs gene expression profiles in specific experimental settings of hippocampal neurogenesis, and also in mouse models with deletion or overexpression of specific genes to reproduce neural pathologies.https://www.frontiersin.org/articles/10.3389/fcell.2025.1605116/fulltranscriptomic analysesRNA sequencingadult neurogenesisagingdentate gyrus stem cellsself-renewal
spellingShingle Laura Micheli
Maurizia Caruso
Giorgio D’Andrea
Daniel Volpe
Manuela Ceccarelli
Felice Tirone
Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
Frontiers in Cell and Developmental Biology
transcriptomic analyses
RNA sequencing
adult neurogenesis
aging
dentate gyrus stem cells
self-renewal
title Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
title_full Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
title_fullStr Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
title_full_unstemmed Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
title_short Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
title_sort survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells
topic transcriptomic analyses
RNA sequencing
adult neurogenesis
aging
dentate gyrus stem cells
self-renewal
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1605116/full
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