Long-term self-renewing stem cells in the adult mouse hippocampus identified by intravital imaging.

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Bottes, Sara 
Pilz, Gregor-Alexander  ORCID logo  https://orcid.org/0000-0002-6161-4976

Neural stem cells (NSCs) generate neurons throughout life in the mammalian hippocampus. However, the potential for long-term self-renewal of individual NSCs within the adult brain remains unclear. We used two-photon microscopy and followed NSCs that were genetically labeled through conditional recombination driven by the regulatory elements of the stem cell-expressed genes GLI family zinc finger 1 (Gli1) or achaete-scute homolog 1 (Ascl1). Through intravital imaging of NSCs and their progeny, we identify a population of Gli1-targeted NSCs showing long-term self-renewal in the adult hippocampus. In contrast, once activated, Ascl1-targeted NSCs undergo limited proliferative activity before they become exhausted. Using single-cell RNA sequencing, we show that Gli1- and Ascl1-targeted cells have highly similar yet distinct transcriptional profiles, supporting the existence of heterogeneous NSC populations with diverse behavioral properties. Thus, we here identify long-term self-renewing NSCs that contribute to the generation of new neurons in the adult hippocampus.

Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Lineage, Female, Gene Expression Profiling, Hippocampus, Homeodomain Proteins, Intravital Microscopy, Male, Metallothionein 3, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Multiphoton, Nerve Regeneration, Nerve Tissue Proteins, Neural Stem Cells, Single-Cell Analysis, Zinc Finger Protein GLI1
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Nat Neurosci
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Springer Science and Business Media LLC
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Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Wellcome Trust