Biology subjects

Gascon, S.

Publications and source records attributed to Gascon, S..

5 recordsLinked to original sources

bioRxiv2025

Modeling the acutely injured brain environment in vitro.

A major challenge to study the regenerative potential of the injured brain is the limited access to this organ in vivo. To address this, we developed an innovative gliosis model that, although established in vitro, originates from a genuine injury in vivo. The model relies on reactive glia acquiring enhanced adhesion, facilitating their rapid adaptation to in vitro conditions, where it faithfully recapitulates key features of brain injury. These include a secretome associated with injury pathways, degenerative responses like neuronal death and neuroinflammation, and regenerative processes such as progenitor proliferation, recruitment and commitment to oligodendrocytes. Moreover, the exposure of adult glial cells to this culture medium recapitulates their acquisition of multipotency observed in both mouse and human injured brains. Finally, our approach allows studying glia-to-neuron reprogramming, a process challenging to tackle in vivo. Consequently, we present a novel tool for exploring stem cell dynamics and regenerative behaviors in CNS pathology.

neuroscience↗

bioRxiv2024

Purinergic Receptor P2Y13 Controls Activation and Mode of Division in Subependymal Adult Neural Stem Cells

The subependymal zone (SEZ) of the mammalian brain is the most active germinal area that continues to generate newborn neurons throughout life. This area harbors a population of neural stem cells (NSCs) that can be found in different states of activation, each differing in proliferative capacity and molecular signature: quiescent NSCs (qNSCs), primed NSCs (pNSCs), and activated NSCs (aNSCs). There is currently a void in terms of the specific markers available to effectively discern between these transient states. Likewise, the molecular signaling mechanisms controlling the transition from quiescence to activation remain largely unexplored, as do the factors influencing the decision between differentiation and self-renewal during NSC division. Here, we present evidence that the metabotropic P2Y13 purinergic receptor plays a critical role in regulating adult neurogenesis. We found that P2Y13 is specifically expressed in NSCs within the adult SEZ and that its levels can be used to distinguish qNSCs from aNSCs. Functionally, P2Y13 signaling promotes NSC activation, enhancing lineage progression, while dampening their self-renewal capacity. Conversely, pharmacological blockade or genetic silencing of the P2Y13 receptor favors NSC quiescence. Thus, we identified the metabotropic P2Y13 purinergic receptor as a pivotal modulator of NSC dynamics, influencing both the balance between NSC quiescence and activation and the mode of NSC division at the subependymal zone.

neuroscience↗

bioRxiv2023

Reprogramming early cortical astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site deficient Ascl1

Cellular reprogramming of mammalian glia to an induced neuronal fate holds potential for restoring diseased brain circuits. While the proneural factor Ascl1 is widely used for neuronal reprogramming, in the early postnatal mouse cortex Ascl1 fails to induce glia-to-neuron conversion, instead promoting proliferation of oligodendrocyte progenitor cells (OPC). Since Ascl1 activity is post-translationally regulated, here we investigated the consequences of mutating six serine phospho-acceptor sites to alanine (Ascl1SA6) on lineage reprogramming in vivo. Ascl1SA6 exhibited increased neurogenic activity in glia of the early postnatal mouse cortex, an effect enhanced by co-expression of Bcl2. Genetic fate-mapping revealed that most induced neurons originated from astrocytes while only a few derived from OPCs. Intriguingly, many Ascl1SA6/Bcl2-induced neurons expressed parvalbumin and were capable of high-frequency action potential firing. Our study demonstrates authentic conversion of astroglia into neurons featuring subclass hallmarks of cortical interneurons, advancing our scope of engineering neuronal fates in the brain.

neuroscience↗

bioRxiv2020

Disentangling metacommunity processes using multiple metrics in space and time

Metacommunity ecology has focused on using observational and analytical approaches to disentangle the role of critical assembly processes, such as dispersal limitation and environmental filtering. Many methods have been proposed for this purpose, most notably multivariate analyses of species abundance and its association with variation in spatial and environmental conditions. These approaches tend to focus on few emergent properties of metacommunities and have largely ignored temporal community dynamics. By doing so, these are limited in their ability to differentiate metacommunity dynamics. Here, we develop a Virtual ecologist approach to evaluate critical metacommunity assembly processes based on a number of summary statistics of community structure across space and time. Specifically, we first simulate metacommunities emphasizing three main processes that underlie metacommunity dynamics (density-independent responses to abiotic conditions, density-dependent biotic interactions, and dispersal). We then calculate a number of commonly used summary statistics of community structure in space and time, and use random forests to evaluate their utility for understanding the strength of these three processes. We found that: (i) time series are necessary to disentangle metacommunity processes, (ii) each of the three studied processes is distinguished with different descriptors, (iii) each summary statistic is differently sensitive to temporal and spatial sampling effort. Some of the most useful statistics include the coefficient of variation of abundances through time and metrics that incorporate variation in the relative abundances (evenness) of species. Surprisingly, we found that when we only used a single snapshot of community variation in space, the most commonly used approaches based on variation partitioning were largely uninformative regarding assembly processes, particularly, variation in dispersal. We conclude that a combination of methods and summary statistics will be necessary to understand the processes that underlie metacommunity assembly through space and time.

ecology↗

bioRxiv2017

Programming of neural progenitors of the adult subependymal zone towards a glutamatergic identity by neurogenin2

While the adult subependymal zone (SEZ) harbors pools of distinct neural stem cells that generate different types of GABAergic interneurons, a small progenitor population in the dorsal SEZ expresses Neurog2 and gives rise to glutamatergic neurons. Here we investigated whether SEZ progenitors can be programmed towards glutamatergic neurogenesis through forced expression of Neurog2. Retrovirus-mediated expression of Neurog2 induced the glutamatergic neuron lineage markers Tbr2 and Tbr1 in cultured SEZ progenitors which subsequently differentiated into functional glutamatergic neurons. Likewise, retrovirus-mediated expression of Neurog2 in dividing SEZ progenitors within the adult SEZ induced Tbr2 and Tbr1 expression, hallmarking entry into the glutamatergic lineage also in vivo. Intriguingly, Neurog2-expressing progenitors failed to enter the rostral migratory stream (RMS) and instead differentiated directly within the SEZ or the adjacent striatum. In sharp contrast, lentivirus-mediated postmitotic expression of Neurog2 failed to reprogram early SEZ neurons, which instead maintained their GABAergic identity and migrated along the RMS towards the olfactory bulb. Thus, our data show that Neurog2 can program SEZ progenitors towards a glutamatergic identity, but fails to reprogram their postmitotic progeny.\n\nSummary statementOur study identifies a critical developmental time window during which progenitors of the adult subependymal zone, specified for generating GABAergic neurons, can be reprogrammed towards glutamatergic neurogenesis.

neuroscience↗