La Manno, GioeleSoldatov, RuslanZeisel, AmitBraun, EmelieHochgerner, HannahPetukhov, ViktorLidschreiber, KatjaKastriti, Maria E.Lönnerberg, PeterFurlan, AlessandroFan, JeanBorm, Lars E.Liu, Zehuavan Bruggen, DavidGuo, JiminHe, XiaolingBarker, RogerSundström, ErikCastelo-Branco, GonçaloCramer, PatrickAdameyko, IgorLinnarsson, StenKharchenko, Peter2022-07-272018-08La Manno, Gioele, Ruslan Soldatov, Amit Zeisel, Emelie Braun, Hannah Hochgerner, Viktor Petukhov, Katja Lidschreiber et al. "RNA Velocity of Single Cells." Nature 560, no. 7719 (2018): 494-498. DOI: 10.1038/s41586-018-0414-60028-08361476-4687https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372883RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena, such as embryogenesis or tissue regeneration. Here we show that RNA velocity—the time derivative of the gene expression state—can be directly estimated by distinguishing unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.en-USResearch Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::GeneticsJournal Article2018-06-1920182022-07-2710.1038/s41586-018-0414-6