Astrogenesis in the murine dentate gyrus is a life-long and dynamic process.
Julia SchneiderJohannes WeigelMarie-Theres WittmannPavel SvehlaSebastian EhrtFang ZhengTarek ElmzzahiJulian KarpfLucía Paniagua-HerranzOnur BasakArif Bülent EkiciAndré ReisChristian AlzheimerFelipe OrtegaSabine LiebscherRuth BeckervordersandforthPublished in: The EMBO journal (2022)
Astrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells. We here combine immunohistochemical approaches with genetic fate-mapping, behavioural paradigms, single-cell transcriptomics, and in vivo two-photon imaging, to comprehensively assess the generation and the proliferation of astrocytes in the dentate gyrus (DG) across the life span of a mouse. Astrogenesis in the DG is initiated by radial glia-like neural stem cells giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside-in-pattern. Also in the adult DG, the vast majority of astrogenesis is mediated through the proliferation of local astrocytes. Interestingly, locally dividing astrocytes were able to adapt their proliferation to environmental and behavioral stimuli revealing an unexpected plasticity. Our study establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamics to hippocampal plasticity.
Keyphrases
- single cell
- signaling pathway
- high resolution
- neural stem cells
- blood brain barrier
- induced apoptosis
- gene expression
- rna seq
- dna methylation
- photodynamic therapy
- high throughput
- cell proliferation
- young adults
- copy number
- cell cycle arrest
- multiple sclerosis
- brain injury
- resting state
- genome wide
- climate change
- endoplasmic reticulum stress
- high density
- human health
- subarachnoid hemorrhage
- childhood cancer