The coding and long noncoding single-cell atlas of the developing human fetal striatum
- 7 May 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 372 (6542), 591-+
- https://doi.org/10.1126/science.abf5759
Abstract
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.Keywords
Funding Information
- CHDI Foundation (grant ID A-11103)
- CHDI Foundation (JSC A11103)
- Wellcome (203151/Z/16/Z)
- Colorado College
- FP7 Coordination of Non-Community Research Programmes (602278)
- FP7 Coordination of Non-Community Research Programmes (2013-17)
- Majlis Keselamatan Negara Malaysia (H2020)
- Majlis Keselamatan Negara Malaysia (874758)
- Majlis Keselamatan Negara Malaysia (2020-23)
- NIHR funding (203151/Z/16/Z)
- WT-MRC cambridge stem cell institute (203151/Z/16/Z)
- NeuroStemCellRepair (FP7, GA no. 602278, 2013-17)
- NSC-Reconstruct (H2020, GA no 874758, 2020-23)
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