A coordinated DNA damage response promotes adult quiescent neural stem cell activation

Autor: Penny A. Jeggo, Limei Ju, Lara Barazzuol
Přispěvatelé: Molecular Neuroscience and Ageing Research (MOLAR), Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cellular differentiation
CHILDHOOD
Apoptosis
Ataxia Telangiectasia Mutated Proteins
Biochemistry
Neural Stem Cells
Animal Cells
Lateral Ventricles
Cell Cycle and Cell Division
Biology (General)
Cell Death
General Neuroscience
Stem Cells
Cell Differentiation
Neural stem cell
3. Good health
Cell biology
Nucleic acids
DIFFERENTIATION
medicine.anatomical_structure
Cell Processes
Stem cell
Cellular Types
General Agricultural and Biological Sciences
Neuronal Differentiation
Research Article
Cell type
SUBVENTRICULAR ZONE
DNA damage
QH301-705.5
Subventricular zone
ORGANIZATION
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Neuroblast
Developmental Neuroscience
medicine
Genetics
Animals
CYCLE
Progenitor cell
Cell Proliferation
General Immunology and Microbiology
X-Rays
Biology and Life Sciences
Neonates
Cell Biology
DNA
MAMMALIAN BRAIN
IRRADIATION
Mice
Inbred C57BL
MICE
030104 developmental biology
Animals
Newborn
nervous system
Cellular Neuroscience
Immunology
RADIATION
Developmental Biology
Neuroscience
Zdroj: PLoS Biology, Vol 15, Iss 5, p e2001264 (2017)
PLoS Biology
PLOS BIOLOGY, 15(5):e2001264. PUBLIC LIBRARY SCIENCE
ISSN: 1545-7885
1544-9173
Popis: Stem and differentiated cells frequently differ in their response to DNA damage, which can determine tissue sensitivity. By exploiting insight into the spatial arrangement of subdomains within the adult neural subventricular zone (SVZ) in vivo, we show distinct responses to ionising radiation (IR) between neural stem and progenitor cells. Further, we reveal different DNA damage responses between neonatal and adult neural stem cells (NSCs). Neural progenitors (transit amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo apoptosis after 2 Gy IR. This response is cell type- rather than proliferation-dependent and does not appear to be driven by distinctions in DNA damage induction or repair capacity. Moreover, exposure to 2 Gy IR promotes proliferation arrest and differentiation in the adult SVZ. These 3 responses are ataxia telangiectasia mutated (ATM)-dependent and promote quiescent NSC (qNSC) activation, which does not occur in the subdomains that lack progenitors. Neuroblasts arising post-IR derive from activated qNSCs rather than irradiated progenitors, minimising damage compounded by replication or mitosis. We propose that rather than conferring sensitive cell death, apoptosis is a form of rapid cell death that serves to remove damaged progenitors and promote qNSC activation. Significantly, analysis of the neonatal (P5) SVZ reveals that although progenitors remain sensitive to apoptosis, they fail to efficiently arrest proliferation. Consequently, their repopulation occurs rapidly from irradiated progenitors rather than via qNSC activation.
Author summary The response of stem cells to DNA damage is poorly understood, although there is increasing evidence that they respond distinctly to differentiated cells. We have monitored the different responses of adult neural stem and progenitor cells to exposure to X-ray irradiation. We see that progenitor cells activate apoptosis, undergo rapid proliferation arrest, and premature differentiation. However, quiescent stem cells do not activate radiation-induced apoptosis. Instead the responses of the progenitor cells promote the activation of these quiescent neural stem cells, thereby replenishing the neuroblasts. These responses and quiescent stem cell activation are dependent on the ataxia telangiectasia mutated (ATM) kinase. We propose that this coordinated response functions to remove damaged progenitor cells and to aid repopulation.
Databáze: OpenAIRE
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