Modes of division and differentiation of neural stem cells

Lazutkin, Alexander; Podgorny, Oleg V.; Enikolopov, Grigori

doi:10.1016/j.bbr.2019.112118

Cited by 48 publications

(42 citation statements)

References 103 publications

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“…Indeed, the depletion rate decreased in proportion to the size of the active NSC pool in juveniles (between 1 and 2 months, Figure 1C, D). However, the depletion rate slowed down considerably more in young adults (between 2 and 6 months of age) and became decoupled from proliferation, so that it became substantially lower than predicted by the disposable stem cell model ( Figure 1D) (Lazutkin et al, 2019). We therefore reasoned that active NSCs may acquire distinct properties in early adulthood that function to slow down depletion and preserve the NSC population.…”

Section: Rapid Nsc Depletion In Juveniles and Reduced Depletion In Admentioning

confidence: 94%

“…Hippocampal NSCs sit atop the lineage hierarchy of neurogenesis and changes in their behaviour are likely involved in the transition towards lower and sustainable levels of neurogenesis during adulthood. However, the behaviour of adult hippocampal NSCs is still not well understood and current divergent models are not yet reconciled (Lazutkin et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Harris

Rigo

Stiehl

et al. 2020

Preprint

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Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilise during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this reduction in stem cell depletion rate is the result of multiple coordinated changes in stem cell behaviour. In particular, while active neural stem cells divide only once or twice before differentiating rapidly in juveniles, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomic, mathematical modelling and label-retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These progressive changes in stem cell behaviour result from reduced expression of the pro-activation protein ASCL1 due to increased post-translational degradation. These mechanisms help reconcile current contradictory models of hippocampal NSC dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species including humans.

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Section: Rapid Nsc Depletion In Juveniles and Reduced Depletion In Admentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Harris

Rigo

Stiehl

et al. 2020

Preprint

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“…While some questions remain, there is consensus that RGL cells undergo a limited number of divisions (most likely three) after which they either revert back to quiescence or terminally differentiate (Bonaguidi, Wheeler et al 2011, Encinas, Michurina et al 2011, Lazutkin, Podgorny et al 2019. In this context it is interesting to note that the ratios of RGL cellcontaining to RGL cell-depleted clones is approximately 3:1 in control mice, suggesting that over the 4-week chase period 1 out of 4 clones differentiated.…”

Section: Zeb1 In Hippocampal Neurogenesis 16mentioning

confidence: 99%

The transcription factor ZEB1 regulates stem cell self-renewal and astroglial fate in the adult hippocampus

Gupta

Errington

Brabletz

et al. 2020

Preprint

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Radial glia-like (RGL) cells persist in the adult mammalian hippocampus where they give rise to new neurons and astrocytes throughout life. Many studies have investigated the process of adult neurogenesis, but factors deciding between neuronal and astroglial fate are incompletely understood. Here, we evaluate the functions of the transcription factor zinc finger E-box binding homeobox 1 (ZEB1) in adult hippocampal RGL cells using a conditional-inducible mouse model. We find that ZEB1 is necessary for self-renewal of active RGL cells as well as for astroglial lineage specification. Genetic deletion of Zeb1 causes differentiation-coupled depletion of RGL cells resulting in an increase of newborn neurons at the expense of newly generated astrocytes. This is due to a shift towards symmetric cell divisions that consume the RGL cell and generate pro-neuronal progenies. We identify ZEB1 as a regulator of stem cell self-renewal and lineage specification in the adult hippocampus.

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“…Adult animal brain is known to have stem cell niches in the ventricular-subventricular zone and the subgranular zone in which new neurons and glial cells are continuously generated from neural stem/progenitor cells (Lazutkin et al, 2019;Obernier and Alvarez-Buylla, 2019). In the subgranular zone of the hippocampus, after exiting the cell cycle, new generations of cells locally migrate to the granular cell layer and turn into mature granular neurons (Lazutkin et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Adult animal brain is known to have stem cell niches in the ventricular–subventricular zone and the subgranular zone in which new neurons and glial cells are continuously generated from neural stem/progenitor cells ( Lazutkin et al, 2019 ; Obernier and Alvarez-Buylla, 2019 ). In the subgranular zone of the hippocampus, after exiting the cell cycle, new generations of cells locally migrate to the granular cell layer and turn into mature granular neurons ( Lazutkin et al, 2019 ). There is also evidence of the presence of additional niches of neural progenitor cells associated with vessels, in particular with pericytes and such regionally activated stem cells also contribute to neural regeneration ( Shimada et al, 2010 , 2012 ; Nakagomi et al, 2011 ; Nakata et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Recombinant Spidroin rS1/9 on Brain Neural Progenitors After Photothrombosis-Induced Ischemia

Moisenovich

Silachev

Moysenovich

et al. 2020

Front. Cell Dev. Biol.

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Modes of division and differentiation of neural stem cells

Cited by 48 publications

References 103 publications

Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

The transcription factor ZEB1 regulates stem cell self-renewal and astroglial fate in the adult hippocampus

Effects of Recombinant Spidroin rS1/9 on Brain Neural Progenitors After Photothrombosis-Induced Ischemia

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