The coding and non-coding RNA single-cell atlas of the human fetal striatum

peer reviewedDeciphering how the human striatum develops is paramount to understand diseases affecting this region. To decode the transcriptional modules that regulate this structure during development we first catalogued 1116, de novo identified, lincRNAs and then profiled 96,789 single-cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (MSNs) arise from a common progenitor and that lineage commitment is established during the post-mitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. In conclusion, our study has delineated the cellular hierarchies governing MSN lineage commitment