Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(5), P. 334 - 354

Published: March 15, 2023

Language: Английский

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Spatially resolved single-cell translatomics at molecular resolution

Science, Journal Year: 2023, Volume and Issue: 380(6652)

Published: June 29, 2023

The precise control of messenger RNA (mRNA) translation is a crucial step in posttranscriptional gene regulation cellular physiology. However, it remains challenge to systematically study mRNA at the transcriptomic scale with spatial and single-cell resolution. Here, we report development ribosome-bound mapping (RIBOmap), highly multiplexed three-dimensional situ profiling method detect translatome. RIBOmap 981 genes HeLa cells revealed cell cycle-dependent translational colocalized functional modules. We mapped 5413 mouse brain tissues, yielding spatially resolved translatomic profiles for 119,173 revealing type-specific region-specific regulation, including remodeling during oligodendrocyte maturation. Our detected widespread patterns localized neuronal glial intact tissue networks.

Language: Английский

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FISH-quant v2: a scalable and modular tool for smFISH image analysis

RNA, Journal Year: 2022, Volume and Issue: 28(6), P. 786 - 795

Published: March 28, 2022

Regulation of RNA abundance and localization is a key step in gene expression control. Single-molecule fluorescence situ hybridization (smFISH) widely used single-cell-single-molecule imaging technique enabling quantitative studies its regulatory mechanisms. Today, these methods are applicable at large scale, which turn come with need for adequate tools data analysis exploration. Here, we present FISH-quant v2, highly modular tool accessible both experts non-experts. Our user-friendly package allows the user to segment nuclei cells, detect isolated RNAs, decompose dense clusters, quantify patterns visualize results single-cell level variations within cell population. This was validated applied on large-scale smFISH image sets, revealing diverse subcellular surprisingly high degree cell-to-cell heterogeneity.

Language: Английский

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RNA‐Targeting Carbon Dots for Live‐Cell Imaging of Granule Dynamics

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(21)

Published: Jan. 16, 2023

Abstract It is significant to monitor the different RNA granules dynamics and phase separation process inside cells under various stresses, for example, oxidative stress. The current small‐molecule probes work well only in fixed usually encounter problems such as insufficient stability biocompatibility, thus a specific RNA‐targeting fluorescent nanoprobe that can be used living urgently desired. Here, de novo design microwave‐assisted synthesis of novel RNA‐targeting, red‐emissive carbon dots (named M‐CDs) are reported by choosing neutral red levofloxacin precursors. as‐synthesized M‐CDs water‐soluble with high fluorescence quantum yield 22.83% selectively bind resulting an enhanced fluorescence. More interestingly, fast internalized into within 5 s real‐time imaging dynamic intracellular stress stress, revealing some characteristics have not been identified previously protein biomarkers. This research paves new pathway visualizing bulk studying phase‐separation behaviors rational terms structure functionality.

Language: Английский

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Mutations linked to neurological disease enhance self-association of low-complexity protein sequences

Science, Journal Year: 2022, Volume and Issue: 377(6601)

Published: June 30, 2022

Protein domains of low sequence complexity do not fold into stable, three-dimensional structures. Nevertheless, proteins with these sequences assist in many aspects cell organization, including assembly nuclear and cytoplasmic structures surrounded by membranes. The dynamic nature cellular assemblies is caused the ability low-complexity (LCDs) to transiently self-associate through labile, cross-β Mechanistic studies useful for study LCD self-association have evolved over past decade form simple assays phase separation. Here, we used such demonstrate that interactions responsible can be dictated labile protein poised close equilibrium between folded unfolded states. Furthermore, missense mutations causing Charcot-Marie-Tooth disease, frontotemporal dementia, Alzheimer's disease manifest their pathophysiology vitro cultured systems enhancing stability otherwise molecular formed upon self-association.

Language: Английский

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RNA granules: functional compartments or incidental condensates?

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 354 - 376

Published: May 1, 2023

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. contain factors for biogenesis and turnover often assumed to represent specialized compartments biochemistry. Recent evidence suggests assemble by phase separation subsoluble ribonucleoprotein (RNP) complexes partially demix from cytoplasm or nucleoplasm. We explore possibility some nonessential condensation by-products arise when RNP exceed their solubility limit as a consequence cellular activity, stress, aging. describe use evolutionary mutational analyses single-molecule techniques distinguish functional "incidental condensates."

Language: Английский

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Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4942 - 4957

Published: Feb. 28, 2023

While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded epitopes liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting that induce FoxP3+ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in dominant allergen, Ara h2. These were inserted downstream an targeting sequence, further endowed vitro with 5′ and 3′ capping sequences, PolyA tail, uridine substitution. Codon-optimized used microfluidics synthesis LNPs ionizable cationic lipid, also decorated lipid-anchored mannose ligand LSEC targeting. Biodistribution confirmed vivo imaging, while ELISpot assays demonstrated increase IL-10-producing Tregs spleen. Prophylactic administration tandem-repeat or combination encapsulated h2 induced effects C3H/HeJ mice, sensitized subsequently challenged crude extract. In addition physical manifestations there suppression Th2-mediated cytokine production, IgE synthesis, mast cell release, accompanied increased IL-10 TGF-β production peritoneum. Similar efficacy during LNP postsensitization. nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. results demonstrate exciting application mRNA/LNP treatment food promise be widely applicable allergy field.

Language: Английский

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De-centralizing the Central Dogma: mRNA translation in space and time

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(3), P. 452 - 468

Published: Jan. 19, 2023

As our understanding of the cell interior has grown, we have come to appreciate that most cellular operations are localized, is, they occur at discrete and identifiable locations or domains. These domains contain enzymes, machines, other components necessary carry out regulate these localized operations. Here, review features one such operation: localization translation mRNAs within subcellular compartments observed across types organisms. We describe conceptual advantages "ingredients" mechanisms local translation. focus on nature mRNAs, how travel get this process is regulated. also evaluate current protein synthesis machines (ribosomes) their cadre regulatory elements, factors.

Language: Английский

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The Tubulin Code, from Molecules to Health and Disease

Annual Review of Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 39(1), P. 331 - 361

Published: Oct. 16, 2023

Microtubules are essential dynamic polymers composed of α/β-tubulin heterodimers. They support intracellular trafficking, cell division, cellular motility, and other processes. In many species, both α-tubulin β-tubulin encoded by multiple genes with distinct expression profiles functionality. further diversified through abundant posttranslational modifications, which added removed a suite enzymes to form complex, stereotyped arrays. The genetic chemical diversity tubulin constitute code that regulates intrinsic microtubule properties is read effectors, such as molecular motors microtubule-associated proteins, provide spatial temporal specificity microtubules in cells. this review, we synthesize the rapidly expanding literature highlight limitations opportunities for field. As complex arrays underlie physiological processes, better understanding how cells employ has important implications human disease ranging from cancer neurological disorders.

Language: Английский

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Tailor made: the art of therapeutic mRNA design

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(1), P. 67 - 83

Published: Nov. 29, 2023

Language: Английский

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