Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity
| Autor: | Sebastian Jessberger, Darcie L. Moore, Mojca Vidmar, Muhammad Khadeesh bin Imtiaz, Raquel A.C. Machado, Sara Bottes, Baptiste N. Jaeger |
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| Přispěvatelé: | University of Zurich, Moore, Darcie L, Jessberger, Sebastian |
| Rok vydání: | 2020 |
| Předmět: |
Aging
Neurogenesis Hippocampus 610 Medicine & health Hippocampal formation Biology 1307 Cell Biology 03 medical and health sciences Mice 0302 clinical medicine Progeria 1311 Genetics Neural Stem Cells Genetics Animals Progenitor cell 030304 developmental biology 0303 health sciences 10242 Brain Research Institute integumentary system Lamin Type B Dentate gyrus Cell Biology Neural stem cell Cell biology nervous system 1313 Molecular Medicine 570 Life sciences biology Molecular Medicine Stem cell 030217 neurology & neurosurgery Lamin |
| Zdroj: | Cell stem cell. 28(5) |
| ISSN: | 1875-9777 |
| Popis: | Summary Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus. With advancing age, levels of neurogenesis sharply drop, which has been associated with a decline in hippocampal memory function. However, cell-intrinsic mechanisms mediating age-related changes in NSC activity remain largely unknown. Here, we show that the nuclear lamina protein lamin B1 (LB1) is downregulated with age in mouse hippocampal NSCs, whereas protein levels of SUN-domain containing protein 1 (SUN1), previously implicated in Hutchinson-Gilford progeria syndrome (HGPS), increase. Balancing the levels of LB1 and SUN1 in aged NSCs restores the strength of the endoplasmic reticulum diffusion barrier that is associated with segregation of aging factors in proliferating NSCs. Virus-based restoration of LB1 expression in aged NSCs enhances stem cell activity in vitro and increases progenitor cell proliferation and neurogenesis in vivo. Thus, we here identify a mechanism that mediates age-related decline of neurogenesis in the mammalian hippocampus. |
| Databáze: | OpenAIRE |
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