Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer DOI Creative Commons
Li Zhang, Yiming Zhang, Chengdi Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Jan. 14, 2022

Abstract Lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing 2342 public bulk sequencing. We investigated their differences in genetic amplification, cellular compositions, expression modules. revealed that LUAD LUSC contained amplifications occurring selectively subclusters AT2 basal cells, had composition modules associated poor survival cancer. Malignant stage-specific gene analyses further uncovered critical transcription factors genes tumor progression. Moreover, identified proliferating differentiating properties cells. Overexpression assays ten genes, including sub-cluster markers AQP5 KPNA2 , indicated functional roles, providing potential targets for early diagnosis

Language: Английский

Confronting false discoveries in single-cell differential expression DOI Creative Commons
Jordan W. Squair, Matthieu Gautier, Claudia Kathe

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 28, 2021

Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available identify differentially expressed genes, principles that distinguish these and their performance remain unclear. Here, we show relative is contingent on ability account for variation between biological replicates. Methods ignore this inevitable biased prone false discoveries. Indeed, most widely used can discover hundreds genes absence differences. To exemplify principles, exposed true discoveries injured mouse spinal cord.

Language: Английский

Citations

611

Best practices for single-cell analysis across modalities DOI Open Access
Lukas Heumos, Anna C. Schaar, Christopher Lance

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 550 - 572

Published: March 31, 2023

Language: Английский

Citations

513

Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data DOI Creative Commons
Aleksandr Ianevski,

Anil K Giri,

Tero Aittokallio

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 10, 2022

Abstract Identification of cell populations often relies on manual annotation clusters using established marker genes. However, the selection genes is a time-consuming process that may lead to sub-optimal annotations as markers must be informative both individual and various types present in sample. Here, we developed computational platform, ScType, which enables fully-automated ultra-fast cell-type identification based solely given scRNA-seq data, along with comprehensive database background information. Using six datasets from human mouse tissues, show how ScType provides unbiased accurate type by guaranteeing specificity positive negative across types. We also demonstrate distinguishes between healthy malignant populations, single-cell calling single-nucleotide variants, making it versatile tool for anticancer applications. The widely applicable method deployed an interactive web-tool ( https://sctype.app ), open-source R-package.

Language: Английский

Citations

411

A harmonized atlas of mouse spinal cord cell types and their spatial organization DOI Creative Commons
D. Russ, Ryan B. Patterson Cross, Li Li

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 29, 2021

Abstract Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases mouse spinal cord have been published in recent years but not integrated together. Here, we generate an atlas types based on single-cell transcriptomic data, unifying available datasets into a common reference framework. We report hierarchical structure postnatal relationships, with location providing highest level organization, then neurotransmitter status, family, and finally, dozens refined populations. validate combinatorial marker code for each neuronal map their spatial distributions adult cord. also show complex lineage relationships among Additionally, develop open-source classifier, SeqSeek, to facilitate standardization identification. This work provides view types, gene expression signatures, organization.

Language: Английский

Citations

182

The neurons that restore walking after paralysis DOI Creative Commons
Claudia Kathe, Michael A. Skinnider, Thomas H. Hutson

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 540 - 547

Published: Nov. 9, 2022

Abstract A spinal cord injury interrupts pathways from the brain and brainstem that project to lumbar cord, leading paralysis. Here we show spatiotemporal epidural electrical stimulation (EES) of 1–3 applied during neurorehabilitation 4,5 (EES REHAB ) restored walking in nine individuals with chronic injury. This recovery involved a reduction neuronal activity humans walking. We hypothesized this unexpected reflects activity-dependent selection specific subpopulations become essential for patient walk after To identify these putative neurons, modelled technological therapeutic features underlying EES mice. single-nucleus RNA sequencing 6–9 spatial transcriptomics 10,11 cords mice chart spatially resolved molecular atlas then employed cell type 12,13 prioritization neurons single population excitatory interneurons nested within intermediate laminae emerged. Although are not required before injury, demonstrate they following Augmenting phenocopied enabled by , whereas ablating them prevented occurs spontaneously moderate thus identified recovery-organizing subpopulation is necessary sufficient regain Moreover, our methodology establishes framework using cartography produce complex behaviours.

Language: Английский

Citations

177

Detection of differentially abundant cell subpopulations in scRNA-seq data DOI Open Access
Jun Zhao, Ariel Jaffe,

Henry Li

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(22)

Published: May 17, 2021

Significance Comparative analysis of samples from two biological states, such as stages embryonic development, is a pressing problem in single-cell RNA sequencing (scRNA-seq). A key challenge to detect cell subpopulations whose abundance differs between the states. To that end, we develop DA-seq, multiscale strategy compare cellular distributions. In contrast existing unsupervised clustering-based analysis, DA-seq can delineate with most significant discrepancy states and potentially reveal important changes processes are undetectable using conventional methods.

Language: Английский

Citations

119

Brain endothelial GSDMD activation mediates inflammatory BBB breakdown DOI
Chao Wei, Wei Jiang, Ruiyu Wang

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8013), P. 893 - 900

Published: April 17, 2024

Language: Английский

Citations

86

Cellular recovery after prolonged warm ischaemia of the whole body DOI
David Andrijević,

Zvonimir Vrselja,

Taras Lysyy

et al.

Nature, Journal Year: 2022, Volume and Issue: 608(7922), P. 405 - 412

Published: Aug. 3, 2022

Language: Английский

Citations

73

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region DOI
Jordan W. Squair, Marco Milano, Alexandra de Coucy

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6664), P. 1338 - 1345

Published: Sept. 21, 2023

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing identify that restore walking after incomplete SCI. We show chemoattracting guiding the transected these neurons region led substantial recovery SCI in mice, whereas simply lesion had no effect. Thus, reestablishing projections characterized forms an essential part axon strategies aimed at lost functions.

Language: Английский

Citations

73

Metformin decelerates aging clock in male monkeys DOI
Yuan‐Han Yang,

Xiaoyong Lu,

Ning Liu

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(22), P. 6358 - 6378.e29

Published: Sept. 12, 2024

Language: Английский

Citations

49