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

Autor: Bottes, Sara, Jaeger, Baptiste N., Pilz, Gregor-Alexander, Jörg, David J., Cole, John Darby, Kruse, Merit, Harris, Lachlan, Korobeynyk, Vladislav I., Mallona, Izaskun, Helmchen, Fritjof, Guillemot, François, Simons, Benjamin D., Jessberger, Sebastian
Zdroj: Nature Neuroscience; February 2021, Vol. 24 Issue: 2 p225-233, 9p
Abstrakt: 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.
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