neural stem cells

Gene regulatory mechanisms of neocortex development and evolution

The neocortex is considered to be the seat of higher cognitive functions in humans. During its evolution, most notably in humans, the neocortex has undergone considerable expansion, which is reflected by an increase in the number of neurons. Neocortical neurons are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behaviour of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development and evolution, neural stem cell regulation and neurodevelopmental disorders.

Exploring mechanisms of human brain expansion in cerebral organoids

The human brain sets us apart as a species, with its size being one of its most striking features. Brain size is largely determined during development as vast numbers of neurons and supportive glia are generated. In an effort to better understand the events that determine the human brain’s cellular makeup, and its size, we use a human model system in a dish, called cerebral organoids. These 3D tissues are generated from pluripotent stem cells through neural differentiation and a supportive 3D microenvironment to generate organoids with the same tissue architecture as the early human fetal brain. Such organoids are allowing us to tackle questions previously impossible with more traditional approaches. Indeed, our recent findings provide insight into regulation of brain size and neuron number across ape species, identifying key stages of early neural stem cell expansion that set up a larger starting cell number to enable the production of increased numbers of neurons. We are also investigating the role of extrinsic regulators in determining numbers and types of neurons produced in the human cerebral cortex. Overall, our findings are pointing to key, human-specific aspects of brain development and function, that have important implications for neurological disease.

Neural stem cells, human-specific genes, and neocortex expansion in development and human evolution

Molecular and cellular mechanisms controlling neural stem cell activity

Neural stem cells (NSCs) generate new neurons throughout life. We use imaging-, genome editing-, and transgenesis-based approaches as well as cellular models of human diseases using pluripotent embryonic cells to study the molecular and cellular framework of NSC biology in the developing and adult brain. Aim of our research is to understand how physiologic and disease-associated alterations of neurogenesis are translated into stem cell-associated plastic changes in the developing and adult brain on a molecular, cellular, and behavioral level.

Neural stem cells as biomarkers of cognitive aging and dementia

Adult hippocampal neurogenesis is implicated in memory formation and mood regulation. The Thuret lab investigates environmental and molecular mechanisms controlling the production of these adult-born neurons and how they impact mental health. We study neurogenesis in healthy ageing as well as in the context of diseases such as Alzheimer’s and depression. By approaching neurogenesis in health and disease, the strategy is two folds: (i) Validating the neurogenic process as a target for prevention and pharmacological interventions. (ii) Developing neurogenesis as a biomarker of disease prediction and progression. In this talk, I will focus on presenting some recent human studies demonstrating how hippocampal neural stem cells fate can be used as biomarkers of cognitive aging and dementia.

Molecular and functional heterogeneity of neural stem cells

Adult neurogenesis in mouse hippocampus

Dr. Aixa V. Morales has been working for more than 20 years in the field of Developmental Biology and from 2005, she is the PI of the laboratory on “Molecular Control of Neurogenesis” at Cajal Institute. Along these years, she has contributed to understanding the control of neurogenesis during development, the dorsoventral specification of neural progenitors, and the temporal control of the migration of neural crest cells. More recently, her lab interest moved towards understanding modulation of adult neurogenesis. Her lab current interest is the control of quiescence, as a mechanism of long-term neural stem cell maintenance in adult niches.

The coming of age of neural stem cells

Novel mechanisms of neurogenesis and neural repair

In order to re-install neurogenesis after loss of neurons upon injury or neurodegeneration, we need to understand the basic principles of neurogenesis. I will first discuss about our discovery of a novel centrosome protein (Camargo et al., 2019) and discuss unpublished work about the great diversity of interphase centrosome proteomes and their relevance for neurodevelopmental disorders. I would then present work on a master regulator of neural stem cell amplification and brain folding (Stahl et al., 2013; Esgleas et al., 2020) to proceed presenting data on utilizing some of these factors for turning astrocytes into neurons. I will present data on the critical role of mitochondria in this conversion process (Gascon et al., 2016, Russo et al., 2020) and how it regulates the speed of conversion also showing unpublished data. If time permits I may touch on recent progress in in vivo reprogramming (Mattugini et al., 2019). Taken together, these data highlight the surprising specificity and importance of organelle diversity from centrosome, nucleolus and mitochondria as key regulators in development and reprogramming.

Stem Cells in the Adult Brain: Regulation and Diversity

Neural stem cells reside in the adult mammalian brain. The ventricular-subventricular zone (V-SVZ) gives rise to olfactory bulb neurons, as well as small numbers of glia throughout life. Adult V-SVZ neural stem cells dynamically integrate intrinsic and extrinsic signals to either maintain the quiescent state or to become activated to divide and generate progeny. I will present our recent findings highlighting adult neural stem cell heterogeneity, including the identification of novel gliogenic domains and cell types, and the key roles of physiological state and long-range signals in the regulation of regionally distinct pools of adult neural stem cells.

Genetic screening and modeling of human-specific neurogenesis in cerebral organoids

“Changing Memory on the Fly, re-evaluation of learned behaviour I n Drosophila” “Metabolic Regulation of Neural Stem Cells” “The answer is in the sauce”

Neural Stem Cell Lineage Progression in Developing Cerebral Cortex

The concerted production of the correct number and diversity of neurons and glia by neural stem cells is essential for intricate neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. We recently performed a clonal analysis by exploiting the genetic MADM (Mosaic Analysis with Double Markers) technology and discovered a high degree of non-stochasticity and thus deterministic mode of RGP behaviour. However, the cellular and molecular mechanisms controlling RGP lineage progression remain unknown. To this end we use quantitative MADM-based genetic paradigms at single cell resolution to define the cell-autonomous functions of signaling pathways controlling cortical neuron/glia genesis and postnatal stem cell behaviour in health and disease. Here I will outline our current understanding of the mechanistic framework instructing neural stem cell lineage progression and discuss new data about the role of genomic imprinting – an epigenetic phenomenon - in cortical development.

Extracellular vesicles from human iPSC-derived neural stem cells alleviate microglial response and cognitive impairments in a chronic neuroinflammation model

"Milking": an innovative approach to investigate the properties of postnatal brain neural stem cells and to obtain oligodendrocyte progenitor cells from live experimental animals

Dysregulation of FLVCR1-dependent mitochondrial calcium handling in neural stem cells causes congenital hydrocephalus

FENS Forum 2024

Manipulating Neural Stem Cells to create a transgenic independent model for glioblastoma

Novel insights into human neural stem cells and adult hippocampal neurogenesis

Nucleoporin 153 deficiency in adult neural stem cells defines a pathological protein-network signature and defective neurogenesis in a mouse model of Alzheimer’s disease

FENS Forum 2024

Cannabidivarin and Neural Stem cells, a new hope for Rett Syndrome?

Extensions of the iOn (integration-coupled On) transgenesis strategy to trace lineage and probe gene function in neural stem cells

Fate of hippocampal neural stem cells at the single cell level during Alzheimer's disease

CETN3 deficiency perturbs proliferation and differentiation of neural stem cells in the developing human cerebral organoids

FENS Forum 2024

Growth/differentiation factor 15 influences primary cilia in neural stem cells in the ventricular-subventricular zone but not in the subgranular zone

Inflammation alters human microglial neurosteroidogenesis with possible impact on neural stem cells differentiation

Investigating the dynamics of activation of postnatal neural stem cells

Investigating the Effects of Ketone Body Supplementation on the Development and Differentiation of Cortical Neural Stem Cells

N-glycosylation of induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) derived from a person with Down Syndrome (DS) caused by Trisomy 21 (T21)

Platelets act as regulators of postnatal Neural Stem Cells of the Subependymal Zone and of the niche microenvironment

Premature aging of Neural Stem Cells in Huntington’s disease

Resident neural stem cells guarantee the regeneration promoted by bulbar olfactory ensheathing cell transplantation after spinal cord injury

Spatio-temporal recruitment of adult neural stem cells during pregnancy for transient neurogenesis

Exploring the potential of induced neural stem cells (iNSCs) as therapy for spinal cord injury in a rat model

FENS Forum 2024

Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells

FENS Forum 2024

Transcriptomic characterization of maturing neurons from human neural stem cells across developmental time points and their application in developmental neurotoxicity screening

FENS Forum 2024

A novel role of MAP1B in neural stem cells reveals their contribution to periventricular heterotopia

FENS Forum 2024

Possible role of NKCC1 in the proliferation of hippocampal neural stem cells during Alzheimer's disease

FENS Forum 2024

Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers

FENS Forum 2024

TET2-mediated regulation of genomic imprinting in adult neural stem cells

FENS Forum 2024

Understanding molecular mechanisms in oligodendrocyte development in vitro using human fetal neural stem cells

FENS Forum 2024

Unravelling the mechanisms behind development of quiescent neural stem cells: The role of Presenilin 1

FENS Forum 2024