PUBLICATION

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

Authors
Labusch, M., Thetiot, M., Than-Trong, E., Morizet, D., Coolen, M., Varet, H., Legendre, R., Ortica, S., Mancini, L., Bally-Cuif, L.
ID
ZDB-PUB-240323-3
Date
2024
Source
Stem Cell Reports   19(4): 515-528 (Journal)
Registered Authors
Bally-Cuif, Laure, Coolen, Marion, Mancini, Laure, Morizet, David, Ortica, Sara, Than-Trong, Emmanuel, Thetiot, Melina
Keywords
Prosaposin, lysosomes, neural stem cell, neurogenesis commitment, pallium, quiescence, zebrafish
Datasets
GEO:GSE239598, GEO:GSE239597, GEO:GSE239594, GEO:GSE225863
MeSH Terms
  • Adult Stem Cells*/metabolism
  • Animals
  • Brain/metabolism
  • Neural Stem Cells*/metabolism
  • Neurogenesis/physiology
  • Saposins/genetics
  • Saposins/metabolism
  • Telencephalon/metabolism
  • Zebrafish/metabolism
PubMed
38518783 Full text @ Stem Cell Reports
Abstract
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. In addition, 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 knockdown 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.
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