Anatomical diversity of the adult corticospinal tract revealed by single cell transcriptional profiling.

Thus, injury, disease, and subsequent degeneration within this pathway result in chronic irreversible functional deficits. Current strategies to repair the damaged CST are sub-optimal in part due to underexplored molecular heterogeneity within the adult tract.

Here we combine spinal retrograde CST tracing with single-cell RNA sequencing in adult male and female mice to index corticospinal neuron (CSN) subtypes that differentially innervate the forelimb and hindlimb. We exploit publicly available datasets to confer anatomical specialization among CSNs and show that CSNs segregate not only along the forelimb and hindlimb axis but also by supraspinal axon collateralization. These anatomically defined transcriptional data allow us to use machine learning tools to build classifiers that discriminate between CSNs and cortical layer 2/3 and non-spinally terminating layer 5 neurons in M1, and separately identify limb specific CSNs.