Summary: Researchers have discovered neural progenitor cells in the meninges.

Source: VIB Flanders.

Possible implications for brain regeneration.

In a cross-domain study directed by professor Peter Carmeliet (VIB – KU Leuven), researchers discovered unexpected cells in the protective membranes that enclose the brain, the so called meninges. These ‘neural progenitors’ – or stem cells that differentiate into different kinds of neurons – are produced during embryonic development. These findings show that the neural progenitors found in the meninges produce new neurons after birth – highlighting the importance of meningeal tissue as well as these cells’ potential in the development of new therapies for brain damage or neurodegeneration. A paper highlighting the results was published in the leading scientific journal Cell Stem Cell.

Scientists’ understanding of brain plasticity, or the ability of the brain to grow, develop, recover from injuries and adapt to changing conditions throughout our lives, has been greatly broadened in recent years. Before the discoveries of the last few decades, neurologists once thought that the brain became ‘static’ after childhood. This dogma has changed, with researchers finding more and more evidence that the brain is capable of healing and regenerating in adulthood, thanks to the presence of stem cells. However, neuronal stem cells were generally believed to only reside within the brain tissue, not in the membranes surrounding it.

The meninges: unappreciated no more:

Believed in the past to serve a mainly protective function to dampen mechanical shocks, the meninges have been historically underappreciated by science as having neurological importance in its own right. The data gathered by the team challenges the current idea that neural precursors – or stem cells that give rise to neurons – can only be found inside actual brain tissue.

Prof. Peter Carmeliet (VIB-KU Leuven): “The neuronal stems cells that we discovered inside the meninges differentiate to full neurons, electrically-active and functionally integrated into the neuronal circuit. To show that the stem cells reside in the meninges, we used the extremely powerful single-cell RNA sequencing technique, a very novel top-notch technique, capable of identifying the (complex gene expression signature) nature of individual cells in a previously unsurpassed manner, a première at VIB.”

Following up on future research avenues:

When it comes to future leads for this discovery, the scientists also see possibilities for translation into clinical application, though future work is required.

Prof. Peter Carmeliet (VIB-KU Leuven): “An intriguing question is whether these neuronal stem cellsin the meninges could lead to better therapies for brain damage or neurodegeneration. However, answering this question would require a better understanding of the molecular mechanisms that regulate the differentiation of these stem cells. How are these meningeal stem cells activated to become different kinds of neurons? Can we therapeutically ‘hijack’ their regeneration potential to restore dying neurons in, for example, Alzheimer’ Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders? Also, can we isolate these neurogenic progenitors from the meninges at birth and use them for later transplantation? These findings open up very exciting research opportunities for the future.”

Unique funding opportunities:

Moving into unchartered territory is high risk, and can offer high gain, but securing funding for such type of research is challenging. However, Carmeliet’s discoveries were made possible to a large extent by funding through “Opening the Future: pioneering without boundaries”, a recently created Mecenas Funding Campaign for funding of high risk brain research but with potential for breakthrough discoveries, started up by the KU Leuven in 2013 and unique in Flanders.

Prof. Peter Carmeliet (VIB-KU Leuven): “Being able to use such non-conventional funding channels is of utmost importance to break new boundaries in research. This unique Mecenas funding initiative by the KU Leuven is innovative and boundary-breaking by itself. Our entire team is enormously grateful for the opportunities it has created for our investigations”.

Source: Sooike Stoops – VIB Flanders
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex” by Francesco Bifari, Ilaria Decimo, Annachiara Pino, Enric Llorens-Bobadilla, Sheng Zhao, Christian Lange, Gabriella Panuccio, Bram Boeckx, Bernard Thienpont, Stefan Vinckier, Sabine Wyns, Ann Bouché, Diether Lambrechts, Michele Giugliano, Mieke Dewerchin, Ana Martin-Villalba, and Peter Carmeliet in Cell Stem Cell. Published online November 23 2016 doi:10.1016/j.stem.2016.10.020

Abstract

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex

Highlights
•Lineage tracing identifies a meningeal neural progenitor (NP) population
•Meningeal NPs migrate from the meninges to the cortex in the neonatal brain
•Meningeal NPs differentiate into functionally integrated cortical neurons
•Single-cell profiling highlights radial glia-like characteristics of meningeal NPs

Summary
Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II–IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.

“Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex” by Francesco Bifari, Ilaria Decimo, Annachiara Pino, Enric Llorens-Bobadilla, Sheng Zhao, Christian Lange, Gabriella Panuccio, Bram Boeckx, Bernard Thienpont, Stefan Vinckier, Sabine Wyns, Ann Bouché, Diether Lambrechts, Michele Giugliano, Mieke Dewerchin, Ana Martin-Villalba, and Peter Carmeliet in Cell Stem Cell. Published online November 23 2016 doi:10.1016/j.stem.2016.10.020