Journal
SCIENCE
Volume 372, Issue 6542, Pages 591-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abf5759
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Funding
- CHDI Foundation [JSC A11103]
- European Union [602278, 874758]
- NIHR funding of the Biomedical Research Centre
- Wellcome Trust [203151/Z/16/Z]
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This research uncovers the cellular hierarchies governing the lineage commitment of MSNs. It found that D1 and D2 medium spiny neurons arise from a common progenitor and lineage commitment is established during the postmitotic transition. Cell type-specific gene regulatory networks were identified and validated through in silico perturbation, while human-specific lincRNAs contributing to the phylogenetic divergence of this structure in humans were also discovered.
Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- and D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic 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. This work delineates the cellular hierarchies governing MSN lineage commitment.
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