PT  - JOURNAL ARTICLE
AU  - Jimena Andersen
AU  - Nicholas Thom
AU  - Jennifer L. Shadrach
AU  - Xiaoyu Chen
AU  - Neal D. Amin
AU  - Se-Jin Yoon
AU  - William J. Greenleaf
AU  - Fabian Müller
AU  - Anca M. Pașca
AU  - Julia A. Kaltschmidt
AU  - Sergiu Pașca
TI  - Landscape of human spinal cord cell type diversity at midgestation
AID  - 10.1101/2021.12.29.473693
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.29.473693
4099  - http://biorxiv.org/content/early/2021/12/29/2021.12.29.473693.short
4100  - http://biorxiv.org/content/early/2021/12/29/2021.12.29.473693.full
AB  - 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.Competing Interest StatementW.J.G. was a consultant for 10x Genomics.