Division-Coupled Astrocytic Differentiation and Age-Related Depletion of Neural Stem Cells in the Adult Hippocampus

By J. Encinas, T. Michurina, N. Peunova, June‐Hee Park, J. Tordo, D. Peterson, G. Fishell, A. Koulakov, G. Enikolopov. 2011

877 citations recorded by the source corpus.

SUMMARY Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool as a consequence of their division may contribute to the age-related decrease in hippocampal neurogenesis. Our results indicate that adult hippocampal stem cells, upon exiting their quiescent state, rapidly undergo a series of asymmetric divisions to produce dividing progeny destined to become neurons and subsequently convert into mature astrocytes. Thus, the decrease in the number of neural stem cells is a division-coupled process and is directly related to their production of new neurons. We present a scheme of the neurogenesis cascade in the adult hippocampus that includes a proposed “disposable stem cell” model and accounts for the disappearance of hippocampal neural stem cells, the appearance of new astrocytes, and the age-related decline in the production of new neurons.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

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Citations in the corpus

Human Hippocampal Neurogenesis Persists throughout Aging (2018, neutral): “GNs are the final product of the differentiation cascade and express neuronal nuclear marker (NeuN), Prox-1, calbindin, and bIII-tubulin (Encinas et al., 2011).”
Neuroinflammation and depression: A review (2020, background): “The birth of new neurons during adulthood undergoes a sequential process, starting with radial neural stem cells (rNSCs), which produce a copy of themselves together with neuroprogenitor (also known as type 2 cells) amplification (Bonaguidi et al., 2011; Encinas et al., 2011).”
Neurogenesis in the Adult Hippocampus. (2015, background): “Encinas and colleagues presented a model in which the potential of the precursor cells is fixed and the precursor cell population becomes exhausted with advancing age (Encinas et al. 2011).”
Extracellular matrix: A dynamic microenvironment for stem cell niche (2014, background): “The intrinsic properties of NSCs present in the SGZ, such as self-renewal and multipotency, are still a matter of debate despite the fact that it was demonstrated that those cells can be isolated and cultured, generating self-renewing cells that can differentiate into neurons [202–205].”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “Critically, the maintenance and activation of these quiescent population of cells appears to be dynamically regulated by experience and aging (Dranovsky et al., 2011; Encinas et al., 2011).”
Experience dictates stem cell fate in the adult hippocampus. (2011, neutral): “into terminal astrocytes suggesting that NSCs are depleted with age (Encinas et al., 2011).”
Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later (2015, background): “In the adult SGZ, one population-level study suggested that NSC activation leads to multiple rounds of proliferation, which is coupled with their depletion via differentiation into astrocytes without their ever returning to quiescence (Encinas et al., 2011).”
Single-cell RNA-seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis (2015, background): “The Nes-CFP reporting system also labeled a small percentage of non-NPCs in the adult dentate gyrus (Figure S1) (Encinas et al., 2011).”
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, neutral): “Alternative RGL properties have also been reported (Encinas et al., 2011; Sierra et al., 2015), suggesting that heterogeneity among RGLs may exist (Gebara et al.”
Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers (2017, background): “Hippocampal stem cells in the rodent brain were reported to possess no means of self-renewal (Encinas et al., 2011), suggesting that a stem cell deficit may underlie the observed progressive decline in neurogenesis with age (Walter et al., 2011; Andersen et al., 2014).”
In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics (2011, neutral): “…recent lineage-tracing study at the population level in the adult hippocampus, which suggests that a nestin+ RGL irreversibly exits the quiescent state to rapidly generate multiple neuronal progeny through asymmetric divisions and subsequently convert into a mature astrocyte (Encinas et al., 2011).”
Sox1 marks an activated neural stem/progenitor cell in the hippocampus (2012, background): “In a third contrasting report, the authors use higher doses of tamoxifen in the nestin-creER model along with real-time expression of nestin (nestin-GFP transgenic mice) and sequential CIdU/IdU staining to arrive at the conclusion that radial astrocytes have a limited lifespan (‘disposable stem cell”