Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance

Nature, Journal Year: 2017, Volume and Issue: 546(7658), P. 431 - 435

Published: June 5, 2017

Language: Английский

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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

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The Self-Organizing Genome: Principles of Genome Architecture and Function

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 28 - 45

Published: Sept. 24, 2020

Language: Английский

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Molecular basis and biological function of variability in spatial genome organization

Science, Journal Year: 2019, Volume and Issue: 365(6457)

Published: Sept. 5, 2019

The complex three-dimensional organization of genomes in the cell nucleus arises from a wide range architectural features including DNA loops, chromatin domains, and higher-order compartments. Although these are universally present most types tissues, recent single-cell biochemistry imaging approaches have demonstrated stochasticity transcription high variability architecture individual cells. We review occurrence, mechanistic basis, functional implications genome organization. summarize observations on cell- allele-specific architecture, discuss nature extrinsic intrinsic sources organization, highlight potential structural heterogeneity for function.

Language: Английский

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Multiplexed single-cell proteomics using SCoPE2

Nature Protocols, Journal Year: 2021, Volume and Issue: 16(12), P. 5398 - 5425

Published: Oct. 29, 2021

Language: Английский

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A Growing Toolbox to Image Gene Expression in Single Cells: Sensitive Approaches for Demanding Challenges

Molecular Cell, Journal Year: 2018, Volume and Issue: 71(3), P. 468 - 480

Published: Aug. 1, 2018

Language: Английский

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Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors

Cell, Journal Year: 2020, Volume and Issue: 182(4), P. 947 - 959.e17

Published: July 30, 2020

Language: Английский

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Principles and mechanisms of non-genetic resistance in cancer

British Journal of Cancer, Journal Year: 2019, Volume and Issue: 122(4), P. 465 - 472

Published: Dec. 13, 2019

Abstract As well as undergoing genetic evolution, cancer cells can alter their epigenetic state to adapt and resist treatment. This non-genetic evolution is emerging a major component of resistance. Only now are we beginning acquire the necessary data tools establish some underlying principles mechanisms that define when, why how resistance occurs. Preliminary studies suggest it exist in number forms, including drug persistence, unstable and, most intriguingly, stable Exactly they each arise remains unclear; however, heterogeneity plasticity appear be important variables. In this review, provide an overview these different forms resistance, before exploring influence emergence. We highlight distinction between Darwinian selection Lamarckian induction discuss capable generating Finally, potential interaction adaptation propose idea ‘the path resistance’, which outlines variables dictate whether cancers through and/or means. Through discussions, hope conceptual framework focuses future studies, whose insights might help prevent or overcome

Language: Английский

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Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes

Cell Reports, Journal Year: 2019, Volume and Issue: 26(5), P. 1174 - 1188.e5

Published: Jan. 1, 2019

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters enhancers of activity-regulated genes. Exactly how modulates these genes has remained unknown. We used single-cell situ transcriptional analysis to show that Fos Npas4 are transcribed stochastic bursts mouse neurons membrane depolarization mRNA expression by increasing burst frequency. then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins mimic block activity-induced locally enhancers. Adding increased prolonging duration resulted higher protein levels an elevation resting potential. Inhibiting reduced reducing frequency impaired experience-dependent induction the hippocampus vivo. Thus, tunes dynamics experience-regulated affect selective changes neuronal cellular function.

Language: Английский

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Single-cell protein analysis by mass spectrometry

Current Opinion in Chemical Biology, Journal Year: 2020, Volume and Issue: 60, P. 1 - 9

Published: June 28, 2020

Language: Английский

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