Biology subjects

Morizet, D.

Publications and source records attributed to Morizet, D..

5 recordsLinked to original sources

bioRxiv2026

Linking transcriptome to cell behavior in real time uncovers molecular fate-asymmetry and a quiescence cycle among adult neural stem cells

Adult neural stem cells (NSCs) are transcriptionally heterogeneous, yet the relationship between molecular heterogeneities and individual NSC trajectories remains unclear. Here, we link transcriptional identities with cellular features and measures of real time to identify molecular trajectories hidden within transcriptomic space. Among self-renewing NSCs, we resolve single-cell molecular transitions associated with fate asymmetry at division. We also show that individual self-renewing NSCs progressively transition from molecular states of deep to shallow quiescence during prolonged quiescence phases. Together, this work reveals individual NSC trajectories within transcriptomic space during fate decisions and state transitions. In particular, it highlights the existence of a transcriptionally encoded quiescence cycle followed by adult NSCs, independent of lineage progression, that balances division with cell growth to sustain self-renewal over time.

developmental biology↗

bioRxiv2026

mTORC1 supports progression toward activation competence in quiescent adult neural stem cells

Neural stem cells (NSCs) sustain lifelong neurogenesis through the tight regulation of quiescence, self-renewal and differentiation. Quiescent NSCs (qNSCs) exist in distinct substates, ranging from deep to shallow quiescence, yet the mechanisms governing these transitions remain unclear. In long-term self-renewing NSCs of the adult zebrafish pallium, we show that mTORC1 activity is specifically enriched during a prolonged quiescence phase in which NSCs acquire activation competence. Functional perturbations, analyzed in situ and using single-cell RNA sequencing, reveal that mTORC1 regulates cell progression during this phase, concomitantly ensuring the correct tempo for NSC transition towards activation and the preservation of stemness. These findings challenge the classical view of mTORC1 as a simple regulator of proliferation and identify it as a key regulator of NSC quiescence heterogeneity and dynamics under physiological conditions. By coordinating stemness maintenance with activation competence, mTORC1 emerges as a central player balancing long-term NSC preservation with neurogenic output in the adult brain.

cell biology↗

bioRxiv2024

Notch signaling blockade links transcriptome heterogeneity in quiescent neural stem cells with their reactivation routes and potential

In the vertebrate brain, neural stem cell (NSC) quiescence is necessary for stemness maintenance. Using single cell RNA sequencing (scRNAseq) in the zebrafish adult telencephalon, we identified different molecular clusters of quiescent NSCs, interpreted to sign different quiescence depths(1). Here, we show that these clusters, when challenged in vivo with an inhibitor of Notch signaling -a major quiescence promoting pathway-, unfold different behaviors. Notably, deeply quiescent NSCs with astrocytic features display a unique activation phenotype that combines the maintenance of astrocytic markers with the rapid upregulation of activation and neuronal commitment genes, reminiscent to murine periventricular astrocytes activating upon lesion. In contrast, an NSC cluster predicted to be in the deepest quiescence state resists Notch blockade, and we demonstrate that the transcription factor Nr2f1b mediates this resistance to activation in vivo. These results together link the molecular heterogeneity of quiescent NSCs with bona fide biological properties and their molecular regulators.

neuroscience↗

bioRxiv2023

Prosaposin maintains adult neural stem cells in a state associated with deep quiescence

In most vertebrates, adult neural stem cells (NSCs) continuously give rise to neurons in discrete brain regions. A critical process for maintaining NSC pools over long periods of time in the adult brain is NSC quiescence, a reversible and tightly regulated state of cell cycle arrest. Recently, lysosomes were identified to regulate the NSC quiescence-proliferation balance. However, it remains controversial whether lysosomal activity promotes NSC proliferation or quiescence, and a finer influence of lysosomal activity on NSC quiescence duration or depth remains unexplored. Using RNA-sequencing and pharmacological manipulations, we show that lysosomes are necessary for NSC quiescence maintenance. Additionally, we reveal that expression of psap, encoding the lysosomal regulator Prosaposin, is enriched in quiescent NSCs (qNSCs) that reside upstream in the NSC lineage and display a deep/long quiescence phase in the adult zebrafish telencephalon. We show that shRNA-mediated psap knock-down increases the proportion of activated NSCs (aNSCs) as well as NSCs that reside in shallower quiescence states (signed by ascl1a and deltaA expression). Collectively, our results identify the lysosomal protein Psap as a (direct or indirect) quiescence regulator and unfold the interplay between lysosomal function and NSC quiescence heterogeneities.

neuroscience↗

bioRxiv2023

Integrative single-cell transcriptomics clarifies adult neurogenesis and macroglia evolution

Macroglia fulfill essential functions in the adult vertebrate brain, producing and maintaining neurons and regulating neuronal communication. However, we still know little about their emergence and diversification. We used the zebrafish D. rerio as a distant vertebrate model with moderate glial diversity as anchor to reanalyze datasets covering over 600 million years of evolution. We identify core features of adult neurogenesis and innovations in the mammalian lineage with a potential link to the rarity of radial glia-like cells in adult humans. Our results also suggest that functions associated with astrocytes originated in a multifunctional cell type fulfilling both neural stem cell and astrocytic functions before these diverged. Finally, we identify conserved elements of macroglial cell identity and function and their time of emergence during evolution. One-Sentence SummaryRadial glia of the adult zebrafish forebrain associate transcriptomic features of adult neural stem cells and astrocytes

neuroscience↗