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Blade-dependent molecular identity and neurogenic potential in the adult dentate gyrus

Bhat, U. A.; Valbuena, S.; Marquez-Galera, A.; Tirado-Melendro, P.; Velotto, M.; Navarron, C. M.; Martins, F.; Doat, H.; Maitre, M.; Rouglan, V.; Leste-Lasserre, T.; Brochard, A.; Morales, A. V.; de la Prida, L. M.; Abrous, D. A.; Lopez-Atalaya, J. P.; Pacary, E.

2026-07-28 neuroscience
10.64898/2026.07.24.740228 bioRxiv
Show abstract

The dentate gyrus (DG) is a key hippocampal gateway for cognition and emotion and a major site of adult neurogenesis, yet its organization along the transverse (suprapyramidal- infrapyramidal) axis remains poorly understood. Here, by integrating bulk RNA sequencing of microdissected mouse DG blades with spatial transcriptomics and single-nucleus RNA sequencing, we define the suprapyramidal and infrapyramidal blades (SB and IB) as distinct molecular compartments characterized by anterior-posterior-dependent gene expression programs. Functionally, the SB exhibits enhanced neurogenic activity, particularly in the anterior DG, including increased progenitor proliferation and neuronal differentiation, whereas the IB contains a larger pool of quiescent neural stem cells. Together, these findings reveal molecular and functional specialization along both transverse and longitudinal axes of the DG and provide a framework for interrogating hippocampal subregional organization in health and disease.

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