Landscape of human spinal cord cell type diversity at midgestation

Abstract

Understanding spinal cord generation and assembly is essential to elucidate how motor behavior is controlled and how disorders arise. The cellular landscape of the human spinal cord remains, however, insufficiently explored. Here, we profiled the midgestation human spinal cord with single cell-resolution and discovered, even at this fetal stage, remarkable heterogeneity across and within cell types. Glia displayed diversity related to positional identity along the dorso-ventral and rostro-caudal axes, while astrocytes with specialized transcriptional programs mapped onto distinct histological domains. We discovered a surprisingly early diversification of alpha (α) and gamma (γ) motor neurons that control and modulate contraction of muscle fibers, which was suggestive of accelerated developmental timing in human spinal cord compared to rodents. Together with mapping of disease-related genes, this transcriptional profile of the developing human spinal cord opens new avenues for interrogating the cellular basis of motor control and related disorders in humans.

Singling out motor neurons in the age of single-cell transcriptomics

“…An exciting future direction in the application of scRNAseq to developmental biology is in understanding differentiation of motor neurons during human development. While experiments involving nonhuman primates are costly, there is ample opportunity to perform descriptive postmortem single-cell transcriptomics and epigenomics during human development [92,93]. Using these techniques, we may garner key insights into the defining features that separate human motor neurons from those of other vertebrates.…”

Dbx1 controls the development of astrocytes of the intermediate spinal cord by modulating Notch signaling

“…Like neuronal subtype specification, astrocyte diversification is highly influenced by the transcriptional code patterning DV progenitors (Hochstim et al, 2008;Muroyama et al, 2005;Vue et al, 2014;Zhao et al, 2014). Interestingly, in line with descriptions in the mouse, a recent analysis of the midgestation human spinal cord have shown astrocytes with specialized DV transcriptional programs and gene expression signatures map also onto distinct anatomical domains (Andersen et al, 2021). In addition, studies in the Drosophila larval ventral nerve cord have shown that individual astrocytes are allocated to consistent positions with their arbors covering stereotyped territories of the neuropil (Peco et al, 2016).…”

Integrative genetic and single cell RNA sequencing analysis provides new clues to the amyotrophic lateral sclerosis neurodegeneration

“…Their study analyzed 17,354 nuclei from adult mouse lumbar spinal cord and founded seven major clusters. The fifth dataset was generated by Andersen et al (2021). Their study obtained transcriptomes of 112,554 cells and 34,884 nuclei from four samples of human spinal cord and indicated the cellular landscape of the human spinal cord, including α and γ MNs.…”