@article{f61f9202ace04242b6424f42d1be9e00,
title = "Astrogenesis in the murine dentate gyrus is a life‐long and dynamic process",
abstract = "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.",
keywords = "astrocytes, development, single cell sequencing, adult neurogenesis, astrogenesis, neural stem cells, voluntary exercise",
author = "Onur Basak",
note = "Funding Information: We thank Chichung Lie and the members of his group for helpful discussions and Chiara Rolando and Michael Wegner as members of J.S.{\textquoteright}s thesis advisory committee for constructive comments on the project. We further thank Marlen Knobloch and Sebastian Jessberger for sharing their clonal analysis data with us, which was important to develop the initial concept of adult astrogenesis. This work was supported by grants from the German Research Foundation (DFG; BE 5136/2-1 and 1-2 to R.B., INST 410/45-1 FUGG). The research training group 2162 “Neurodevelopment and Vulnerability of the Central Nervous System” of the German Research Foundation (DFG GRK2162/1) supported this work as follows: J.S as an associated fellow and M.-T.W. and J.K. as fellows of the GRK2162. J.W. was supported by the Interdisciplinary Centre for Clinical Research (IZKF), Erlangen. S.L. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology—EXC 2145 SyNergy—ID 390857198 and the Emmy Noether Programme. P.S. was supported by the Graduate School for Systemic Neurosciences GSN-LMU. Felipe Ortega acknowledges grants from the local Government of Madrid (Comunidad de Madrid, Spain) under the Multiannual Agreement with the Universidad Complutense through the Program to Stimulate Research for Young Doctors in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) UCM-CAM (PR65/19-22453) and from the Spanish Ministerio de Ciencia, Innovaci{\'o}n y Universidades (MCIU, PID2019-109155RB-I00, BFU2015-70067REDC). The present work was performed in fulfillment of the requirements for obtaining the degree “Dr. med.” to Johannes Weigel. Open access funding enabled and organized by Projekt DEAL. Funding Information: We thank Chichung Lie and the members of his group for helpful discussions and Chiara Rolando and Michael Wegner as members of J.S.{\textquoteright}s thesis advisory committee for constructive comments on the project. We further thank Marlen Knobloch and Sebastian Jessberger for sharing their clonal analysis data with us, which was important to develop the initial concept of adult astrogenesis. This work was supported by grants from the German Research Foundation (DFG; BE 5136/2‐1 and 1‐2 to R.B., INST 410/45‐1 FUGG). The research training group 2162 “Neurodevelopment and Vulnerability of the Central Nervous System” of the German Research Foundation (DFG GRK2162/1) supported this work as follows: J.S as an associated fellow and M.‐T.W. and J.K. as fellows of the GRK2162. J.W. was supported by the Interdisciplinary Centre for Clinical Research (IZKF), Erlangen. S.L. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology—EXC 2145 SyNergy—ID 390857198 and the Emmy Noether Programme. P.S. was supported by the Graduate School for Systemic Neurosciences GSN‐LMU. Felipe Ortega acknowledges grants from the local Government of Madrid (Comunidad de Madrid, Spain) under the Multiannual Agreement with the Universidad Complutense through the Program to Stimulate Research for Young Doctors in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) UCM‐CAM (PR65/19‐22453) and from the Spanish Ministerio de Ciencia, Innovaci{\'o}n y Universidades (MCIU, PID2019‐109155RB‐I00, BFU2015‐70067REDC). The present work was performed in fulfillment of the requirements for obtaining the degree “Dr. med.{"} to Johannes Weigel . Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",
year = "2022",
month = jun,
day = "1",
doi = "10.15252/embj.2021110409",
language = "English",
volume = "41",
pages = "1--27",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "11",
}