mRNAs, proteins and the emerging principles of gene expression control

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(10), P. 630 - 644

Published: July 24, 2020

Language: Английский

---

SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation

Genome biology, Journal Year: 2018, Volume and Issue: 19(1)

Published: Oct. 9, 2018

Some exciting biological questions require quantifying thousands of proteins in single cells. To achieve this goal, we develop Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) and validate its ability to identify distinct human cancer cell types based on their proteomes. We use SCoPE-MS quantify over a thousand differentiating mouse embryonic stem The single-cell proteomes enable us deconstruct populations infer protein abundance relationships. Comparison between transcriptomes indicates coordinated mRNA covariation, yet many genes exhibit functionally concerted regulatory patterns at the level.

Language: Английский

---

Lineage tracing meets single-cell omics: opportunities and challenges

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(7), P. 410 - 427

Published: March 31, 2020

Language: Английский

---

The technological landscape and applications of single-cell multi-omics

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 695 - 713

Published: June 6, 2023

Language: Английский

---

Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Jan. 27, 2021

Abstract Background Macrophages are innate immune cells with diverse functional and molecular phenotypes. This diversity is largely unexplored at the level of single-cell proteomes because limitations quantitative protein analysis. Results To overcome this limitation, we develop SCoPE2, which substantially increases accuracy throughput while lowering cost hands-on time by introducing automated miniaturized sample preparation. These advances enable us to analyze emergence cellular heterogeneity as homogeneous monocytes differentiate into macrophage-like in absence polarizing cytokines. SCoPE2 quantifies over 3042 proteins 1490 single macrophages 10 days instrument time, quantified allow discern cell type. Furthermore, data uncover a continuous gradient proteome states for macrophages, suggesting that macrophage may emerge Parallel measurements transcripts 10× Genomics suggest our 20-fold more copies than RNA per gene, thus, supports quantification improved count statistics. allowed exploring regulatory interactions, such interactions between tumor suppressor p53, its transcript, genes regulated p53. Conclusions Even environment, heterogeneous. correlates inflammatory axis classically alternatively activated macrophages. Our methodology lays foundation analysis mass spectrometry demonstrates potential inferring transcriptional post-transcriptional regulation from variability across cells.

Language: Английский

---

Ultra‐high sensitivity mass spectrometry quantifies single‐cell proteome changes upon perturbation

Molecular Systems Biology, Journal Year: 2022, Volume and Issue: 18(3)

Published: Feb. 28, 2022

Language: Английский

---

Spatial heterogeneity in the mammalian liver

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2019, Volume and Issue: 16(7), P. 395 - 410

Published: April 1, 2019

Language: Английский

---

SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(10), P. e55 - e55

Published: March 10, 2020

Single-cell transcriptomics offers unprecedented opportunities to infer the ligand-receptor (LR) interactions underlying cellular networks. We introduce a new, curated LR database and novel regularized score perform such inferences. For first time, we try assess confidence in predicted show that our outperforms other scoring schemes while controlling false positives. SingleCellSignalR is implemented as an open-access R package accessible entry-level users available from https://github.com/SCA-IRCM. Analysis results come variety of tabular graphical formats. instance, provide unique network view integrating all intercellular interactions, function relating receptors expressed intracellular pathways. A detailed comparison related tools conducted. Among various examples, demonstrate on mouse epidermis data discover oriented communication structure external basal layers.

Language: Английский

---

Single-cell Proteomics: Progress and Prospects

Molecular & Cellular Proteomics, Journal Year: 2020, Volume and Issue: 19(11), P. 1739 - 1748

Published: Aug. 26, 2020

MS-based proteome profiling has become increasingly comprehensive and quantitative, yet a persistent shortcoming been the relatively large samples required to achieve an in-depth measurement. Such bulk samples, typically comprising thousands of cells or more, provide population average obscure important cellular heterogeneity. Single-cell proteomics capabilities have potential transform biomedical research enable understanding biological systems with new level granularity. Recent advances in sample processing, separations MS instrumentation now make it possible quantify >1000 proteins from individual mammalian cells, coverage that input just few years ago. This review discusses factors parameters should be optimized across workflow for single-cell other low-input measurements. It also highlights recent developments advanced field opportunities further development.

Language: Английский

---

Quantitative single-cell proteomics as a tool to characterize cellular hierarchies

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

Published: June 7, 2021

Large-scale single-cell analyses are of fundamental importance in order to capture biological heterogeneity within complex cell systems, but have largely been limited RNA-based technologies. Here we present a comprehensive benchmarked experimental and computational workflow, which establishes global mass spectrometry-based proteomics as tool for large-scale analyses. By exploiting primary leukemia model system, demonstrate both through pre-enrichment populations non-enriched unbiased approach that our workflow enables the exploration cellular this aberrant developmental hierarchy. Our is capable consistently quantifying ~1000 proteins per across thousands individual cells using instrument time. Furthermore, develop (SCeptre) effectively normalizes data, integrates available FACS data facilitates downstream analysis. The presented here lays foundation implementing studies world.

Language: Английский

---