Project description

Recent advances in single cell omics approaches are revolutionizing the current knowledge of biological processes occurring in both physiological and pathological conditions. In the IiF proposal “Targeting Pericyte-like Cells for Functional Regeneration - Lessons learned from Tendon, Spinal Cord and Optic Nerve Injuries Project No.2022-IiF-006-Tempfer”, a collaboration between the Institute of Tendon and Bone Regeneration, the Institute of Molecular Regenerative Medicine, the University Clinic of Ophthalmology and Optometry and the University of Helsinki, single nuclei RNA sequencing (snRNAseq) analysis was proposed to understand the role of pericytes in non-regenerative and regenerative healing.
Pericytes (PCs) are perivascular cells that have the potential to contribute to tissue repair and regenerative processes in the central nervous system (CNS). The major pathological hallmark of multiple sclerosis (MS), a debilitating disease that affects various functions of the CNS, is the loss of myelin-forming oligodendrocytes, resulting in demyelination of the nerve fibers. One of the proposed therapeutic targets for MS is the remyelination, a regenerative process aimed at restoring the myelin sheath surrounding nerves.
Recently, we have demonstrated a potential remyelinating effect of PCs, both in vitro and in vivo. Therefore, assessing the molecular signature of PC subpopulations involved in the remyelination process by snRNAseq will potentially define a novel targets to promote a PC-mediated therapies in MS and other demyelinating diseases of the CNS.
The applicant of this PMU-FIZ Talent Pool application, Dr. Marco Zattoni, PostDoc at the Institute of Molecular Regenerative Medicine, is heavily involved in the bioinformatic analysis of the snRNAseq data. He is also actively involved in the experimental design for the subsequent analysis of the IiF proposal “2022-IiF-006-Tempfer”.
The aim of the present proposal stems from a biological question that may remain unanswered if the analysis is limited to snRNAseq. Indeed, the tissue distribution of different PC subpopulations could be affected during the remyelination process. Therefore, the addition of a spatial transcriptomic analysis (Nature “method of the year 2020”), on healthy and lesioned spinal cord tissue, will allow further exploration of the gene expression signature of PCs at the single cell level together with their spatial location.
Our analysis will allow the spatial definition of de/remyelination-specific subpopulations of PCs. It will also facilitate the immunohistochemistry-based confirmation of the snRNAseq-derived markers of different PC subpopulations at the protein level.