Single‐cell analysis reveals dynamic changes of neural cells in developing human spinal cord

Abstract

During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFRexpressing transitional glial cells exhibited a unique positionspecific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.

A Cellular Taxonomy of the Adult Human Spinal Cord

“…Rayon and colleagues 25 , focused on first trimester spinal cord derived from four human embryos, and identified diverse progenitor and neuronal populations, and performed a systematic comparison with the spinal cord cell types of the developing mouse spinal cord. Zhang and colleagues 26 profiled the early and mid-stages of fetal development with an important focus on glial development and cell-cell communication. For the adult human spinal cord, Zhang and colleagues performed single nucleus RNA-seq on the spinal cord from two donors and identified glial and neuronal cell types among 15,811 nuclei 27 .…”

“…We created a molecular catalog of the human lumbar spinal cord to investigate how specialized transcriptional repertoires of spinal cord cell types could endow them with their particular cellular features and functions. Recent papers have used single cell sequencing to identify human spinal cord cell types from embryonic tissue and an unpublished pre-print reports a single cell sequencing characterization of adult spinal cord tissue [25][26][27] . However, none of these studies examined motoneurons in detail or the expression patterns of genes associated with neurodegenerative disease, leaving the question of differential vulnerability of specific cell types unaddressed.…”

“…Thus, prior work has only been done on limited cell types or in human fetal tissue (Rayon et al, 2021;D. Zhang et al, 2021;Q. Zhang et al, 2021).…”

Decoding spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin

“…Different neurons, including ExNs (e.g. showed that glial cells first appeared at W7-8 6 , equivalent to mouse embryonic day (E) 14-16. However, we observed that all glial cell markers were expressed at W5, in which we found that ASCs (MSX1+GFAP+) were derived from the dorsal ventricular zone, EPCs These subpopulations or cell states could be distinguished with single or combinatorial markers (Supplementary Figure 2).…”

“…To compare cell type differences across species, timepoints, and technologies, we performed stepwise data integration to integrate our human scRNA-seq data with publicly available scRNA-seq datasets of spinal cord samples, including human development 6,7 , mouse embryonic development 19 , mouse postnatal development 20 , mouse adulthood [30][31][32][33][34] and datasets suggested in a meta-analysis of mouse spinal cord atlases 35 . We created an integrated cell atlas with these 1.8 million cells (Fig 7a-c).…”