Periodic Reporting for period 2 - OLI.VAS (The Oligo-Vascular interface: understanding its properties and functions)
Reporting period: 2022-02-01 to 2023-07-31
Despite neurons being the most studied cell type of the central nervous system (CNS), this is also composed
of glia and blood vessels. Research of the last decade has brought these two cellular components into focus
and highlighted the need of studying all cellular compartments of the CNS as a whole, as well as their intercellular
communication, for better understanding CNS development, function and pathology. Still, despite the
fact that the human brain contains as many blood vessels as neurons, until very recently the CNS vasculature
has been an overlooked component of the CNS. We and others could recently show that in the CNS,
communication between neural stem cells, neuronal progenitors, neurons and microglia to endothelial cells
(ECs) is critical for proper blood vessel development and homeostatic maintenance. Blood vessel
dysfunction is an early event in multiple neurodegenerative disorders, justifying the need for a better
understanding of the CNS vasculature to tackle those diseases.
Myelin (made by oligodendrocytes (OLs) in the CNS) is a lipid-rich membrane sheath that wraps, insulate and
provides metabolic support to axons. Despite the severe outcome of demyelinating diseases such as neonatal
white matter injury or multiple sclerosis (MS), little is known about the mechanisms by which myelin is
disrupted or not formed properly or how remyelination, which often fails in pathological conditions, can be
facilitated.
With the new concept of an oligo-vascular interface (OLI.VAS) we refer to the unique inter-relationship
between OPCs/OLs and the vasculature.
The overall aim of this project is to understand how blood vessels and oligodendrocyte cells interact and to leverage this knowlege to better understand white matter diseases.
These project promise to address central questions at the edge of the research fields of neurobiology and vascular
biology. The synergy between each part of the proposal will generate unprecedented insight into the
contribution of the vasculature to demyelinating disorders from the innovative point of view of considering
it as a signaling platform. Ultimately, our multi-scale analysis of the oligo-vascular interface will provide new
opportunities to promote remyelination in white matter diseases such as MS, one of the world’s most common
neurological conditions, which currently affects more than 600.000 people in Europe.
Completion of this
project will also impact on the future research perspective in the field of neurodegenerative diseases as it
will open the option to consider the use of engineered vascular cells as cell therapy, or of their derived signals,
to prevent or treat those pathologies.
of glia and blood vessels. Research of the last decade has brought these two cellular components into focus
and highlighted the need of studying all cellular compartments of the CNS as a whole, as well as their intercellular
communication, for better understanding CNS development, function and pathology. Still, despite the
fact that the human brain contains as many blood vessels as neurons, until very recently the CNS vasculature
has been an overlooked component of the CNS. We and others could recently show that in the CNS,
communication between neural stem cells, neuronal progenitors, neurons and microglia to endothelial cells
(ECs) is critical for proper blood vessel development and homeostatic maintenance. Blood vessel
dysfunction is an early event in multiple neurodegenerative disorders, justifying the need for a better
understanding of the CNS vasculature to tackle those diseases.
Myelin (made by oligodendrocytes (OLs) in the CNS) is a lipid-rich membrane sheath that wraps, insulate and
provides metabolic support to axons. Despite the severe outcome of demyelinating diseases such as neonatal
white matter injury or multiple sclerosis (MS), little is known about the mechanisms by which myelin is
disrupted or not formed properly or how remyelination, which often fails in pathological conditions, can be
facilitated.
With the new concept of an oligo-vascular interface (OLI.VAS) we refer to the unique inter-relationship
between OPCs/OLs and the vasculature.
The overall aim of this project is to understand how blood vessels and oligodendrocyte cells interact and to leverage this knowlege to better understand white matter diseases.
These project promise to address central questions at the edge of the research fields of neurobiology and vascular
biology. The synergy between each part of the proposal will generate unprecedented insight into the
contribution of the vasculature to demyelinating disorders from the innovative point of view of considering
it as a signaling platform. Ultimately, our multi-scale analysis of the oligo-vascular interface will provide new
opportunities to promote remyelination in white matter diseases such as MS, one of the world’s most common
neurological conditions, which currently affects more than 600.000 people in Europe.
Completion of this
project will also impact on the future research perspective in the field of neurodegenerative diseases as it
will open the option to consider the use of engineered vascular cells as cell therapy, or of their derived signals,
to prevent or treat those pathologies.
From the begining of the project we have:
- Analyzed several data sets of scRNAseq data of human MS patients, as well as models of white matter injury in mice. This has generated a list of potential candidates mediating the communication between endothelial cells and cells of the oligodendrocyte lineage that we are taking now for validation and characterization.
- Generated the first samples for sequencing of blood vessels and their associated cells during mouse development
- Generated sequencing data of genes being translated in endothelial cells during brain development
- identify that the endothelial derived factor Angiopoietin 2 is specifically upregulated in white matter upon injury - we are further characterizing it functionality.
- Analyzed several data sets of scRNAseq data of human MS patients, as well as models of white matter injury in mice. This has generated a list of potential candidates mediating the communication between endothelial cells and cells of the oligodendrocyte lineage that we are taking now for validation and characterization.
- Generated the first samples for sequencing of blood vessels and their associated cells during mouse development
- Generated sequencing data of genes being translated in endothelial cells during brain development
- identify that the endothelial derived factor Angiopoietin 2 is specifically upregulated in white matter upon injury - we are further characterizing it functionality.
Progress made is less than expected due to COVID pandemia.
At the end of the project we expect that we will have a complete understanding of the role of blood vessels in white matter diseases
At the end of the project we expect that we will have a complete understanding of the role of blood vessels in white matter diseases