ECtomics · Dissecting spinal cord ependymal cell heterogeneity by single-cell transcriptomics

Dissecting spinal cord ependymal cell heterogeneity by single-cell transcriptomics

Lining the central canal of the adult spinal cord, specialised cells called ependymal cells (ECs) perform a number of functions that are essential for proper functioning of the tissue. Besides forming a physical barrier between the cerebrospinal fluid (CSF) and the nervous system, ECs help to propel the CSF, which flows from the brain ventricles through the spinal cord central canal distributing signals and molecules between cells and collecting waste products. ECs also regulate CSF composition by secreting molecules into it and scavenging harmful substances from it. But perhaps what has put spinal cord ECs in the limelight is their ability to behave as neural stem cells – this is to self-renew and give rise to other specialised cell types. Despite this, the ability to resolve spinal cord injuries in mammals is limited; and spinal cord injury leads to permanent disability. Only in Europe, over 300,000 people are affected and every year there are between 250,000 and 500,000 new cases of spinal cord injury worldwide resulting from trauma, from disease or degeneration. A close look at the central canal is enough to see that ECs are heterogeneous. Based on their shape, ECs are classified in three subtypes: tanycytes, which typically enwrap blood vessels; radial ECs, which resemble embryonic stem/progenitor cells of the nervous system and locate exclusively to the dorsal and ventral poles of the central canal; and the most abundant cuboidal ECs. ECs also vary at the molecular level, with specific proteins detected only in subsets of ECs. Due to limitations of traditional methods, requiring many cells as input or based on only a handful of cherry-picked molecular markers, it remained unclear whether this heterogeneity reflects functional differences between ECs or different maturation states; and the precise identity of the spinal cord stem cell is still elusive. Recent advances in single-cell RNA-sequencing (scRNA-seq) technologies make it possible for the first time to sequence thousands of RNA transcripts within a cell. The transcriptome of a cell can then be interpreted as its proof of identity and inform about its function. The overall objective of this project is the comprehensive characterisation of spinal cord ECs using scRNA-seq, and to map computationally-defined ependymal subtypes back onto the tissue. This research is a necessary step for investigating the function and potential of different spinal cord EC subtypes and may inspire new therapeutic strategies to, in the future, promote spinal cord repair.

Data: CORDIS, © European Union