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Open AccessJournal ArticleDOI

RNA velocity of single cells

TLDR
It is shown that RNA velocity—the time derivative of the gene expression state—can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA sequencing protocols, and expected to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.
Abstract
RNA 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 between 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.

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A generalization of t-SNE and UMAP to single-cell multimodal omics

TL;DR: In this article, the relative contribution of each modality to a concise representation of cellular identity is automatically learned, which promotes discriminative features but suppresses noise, and produces unified embeddings that better match known cell types and harmonize RNA and protein velocity landscapes.
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Effect of intra- and inter-tumoral heterogeneity on molecular characteristics of primary IDH-wild type glioblastoma revealed by single-cell analysis

TL;DR: To reveal the effects of intra‐ and inter‐tumoral heterogeneity on characteristics of primary IDH‐wild type glioblastoma cells, a large number of experiments were conducted on single patients with or without prior treatment with chemotherapy.
Journal ArticleDOI

High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells.

TL;DR: A comprehensive account of HFSC molecular heterogeneity during their self‐renewing stage is provided, which enables future HF functional studies.
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Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop.

TL;DR: Topalian et al. as discussed by the authors demonstrated that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTβR) signaling.
References
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Journal ArticleDOI

Genome-wide atlas of gene expression in the adult mouse brain

Ed S. Lein, +109 more
- 11 Jan 2007 - 
TL;DR: An anatomically comprehensive digital atlas containing the expression patterns of ∼20,000 genes in the adult mouse brain is described, providing an open, primary data resource for a wide variety of further studies concerning brain organization and function.
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Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells

TL;DR: This work has developed a high-throughput droplet-microfluidic approach for barcoding the RNA from thousands of individual cells for subsequent analysis by next-generation sequencing, which shows a surprisingly low noise profile and is readily adaptable to other sequencing-based assays.
Journal ArticleDOI

The glial nature of embryonic and adult neural stem cells

TL;DR: The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated.
Journal ArticleDOI

Smart-seq2 for sensitive full-length transcriptome profiling in single cells

TL;DR: Smart-seq2 with improved reverse transcription, template switching and preamplification to increase both yield and length of cDNA libraries generated from individual cells to improve detection, coverage, bias and accuracy.
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