Speaker
Description
"Initial evidence for adult neurogenesis in the mammalian brain was already obtained in the 60s of the last century, when newly generated neurons were first described in the rat brain (Altman, 1962). Since then, numerous studies have provided experimental evidence of adult neurogenesis in several mammalian species, from rodents to non-human primates and humans. Despite the extensive characterization of neural stem cells (NSCs) in the adult brain, still relatively little is known about their origin.
Here, we investigate the regulatory mechanisms underlying adult NSCs (aNSCs) specification in the mouse Ventricular Sub-Ventricular Zone (V-SVZ) and explore the ontogeny of aNSCs across different mammalian species.
The majority of the aNSCs in the mouse V-SVZ is set aside during a specific window of the embryonic development (E13.5-E16.5) from slowly dividing progenitor cells (Furutachi et al., 2015; Fuentalba et al., 2015). To characterize the embryonic ancestors of aNSCs, we isolated slowly and fast dividing LGE progenitors from the iCOUNT mouse line (Denoth-Lippurner et al., 2021) and profiled their transcriptome via single-cell RNA sequencing. We identified distinct clusters of stem/progenitor cells. Via differential gene expression analysis, we detected a set of transcripts enriched in slowly versus fast dividing progenitors. We selected several candidates and explored their function in aNSCs specification via loss of function analysis, which will be presented at the meeting.
Finally, to address whether the establishment of aNSCs occurs similarly in other mammals, we performed cross-species comparison of single-cell datasets from the mouse, ferret and human embryonic brain, with the aim to identify a common molecular signature of the embryonic ancestors of aNSCs.
Taken together, our work aims to identify the molecular mechanisms specifying aNSCs with the long-term aim to possibly elicit their specification also in other brain regions lacking adult neurogenesis."
| Author(s) | Daniela Cimino *1,2,3, Virginia Fernández 4, Annina Denoth-Lippurner 5, Anna Danese 1,2, Tatiana Simon-Ebert 1,2, Sebastian Jessberger 5, Victor Borrell 4, Magdalena Götz 1,2 |
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| Affiliation(s) | "1 Biomedical Center (BMC), Division of Physiological Genomics, Faculty of Medicine, Ludwig-Maximilian University Munich, Planegg-Martinsried Germany, 2 Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Institute of Stem Cell Research, BMC, Planegg-Martinsried, Germany, 3 Graduate School of Systemic Neurosciences, LMU, Plannegg-Martinsried, Germany, 4 Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d’Alacant 03550, Spain, 5 Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland" |
