"Spatial and Molecular Consensus Atlas of Spinal Cord Cell Types in Mouse, Macaque, and Human"

"The spinal cord contains evolutionarily conserved cell types critical for motor function, sensory processing, and autonomic regulation, many of which are implicated in diverse neurological diseases and injuries. Yet, the field lacks a comprehensive molecular characterization of cellular diversity in the human, macaque, and mouse spinal cord. We present a unified, cross-species cell type atlas based on the integration of single-nucleus gene expression, chromatin accessibility, and spatial transcriptomic data from cervical, thoracic, lumbar, and sacral levels, including motor neurons sampled across the entire rostro-caudal axis of the macaque spinal cord. We generated a cell type-guided anatomical map of spinal cord laminae and nuclei by leveraging the spatial distributions of molecularly defined cell types. Cell types were aligned with anatomically defined populations implicated in sensory processing and disease. We identified both conserved and species-specific cellular features, including specialized gene expression across distinct motor neuron subtypes. Finally, we dissected the enhancer logic underlying viral targeting of disease-associated cell types using cross-species cis-regulatory analysis and deep learning models that uncovered conserved regulatory grammar encoding cell identity. Together, these results establish a unifying molecular and anatomical taxonomy of spinal cord cell types across species and define cross-species correspondences among vulnerable cell types implicated in human disease."

Data citation

No data citation listed

Funding agency

NIMH

Grant numbers

UM1MH130981

Access

open

License

CC BY 4.0