Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning

ABSTRACT: Efficient and accurate nanocarrier development for targeted drug delivery is hindered by the inability to analyze cell-level biodistribution across intact whole organisms. We introduce SCP-Nano (Single Cell Precision Nanocarrier Identification), a deep learning pipeline designed to quantify the targeting of millions of cells by nanocarriers in whole-mouse bodies imaged at cellular resolution. SCP-Nano revealed the tissue distribution patterns of lipid nanoparticles (LNPs) following different injection routes at doses as low as 0.0005 mg/kg—far below the detection limits of conventional whole-body imaging techniques. Notably, we demonstrated that LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to changes in the heart's protein composition that suggest immune activation and possible blood vessel damage. Additionally, we showed that SCP-Nano can analyze various types of nanocarriers, including liposomes, polyplexes, DNA origami, and adeno-associated viruses (AAVs). SCP-Nano's high sensitivity enables accurate 3D mapping of nanocarrier distribution throughout mouse bodies, even detecting very low levels in unexpected tissues. SCP-Nano is poised to accelerate the development of precise and safe nanocarrier-based therapeutics.

INSTRUMENT(S): timsTOF SCP

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Ali Erturk

LAB HEAD: Prof. Ali

PROVIDER: PXD056871 | Pride | 2024-12-06

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	FPbase_EGFP_uniprotkb_proteome_UP000000589_AND_revi_2024_03_01_MUS_CANONICAL_17k_proteins.fasta	Fasta
	LNP_plasma_corona_BioNTech.zip	Other
	LNP_plasma_corona_LungSORT.zip	Other
	LNP_plasma_corona_MC3.zip	Other
	LNP_plasma_corona_PBSctrl.zip	Other

Items per page:

1 - 5 of 27

Similar Datasets

Expression data from murine cardiac tissue

Project description:Gender dimorphism exists in the physiological response to diet and other environmental factors. Trans-hydrogenated fatty acid (TFA) intake is associated with an increase in coronary heart disease (CHD), and gender differences in the incidence of CHD are well documented. Neonatal administration of Monosodium Glutamate (MSG) causes stunted heart growth and hypoplasticity; and gender dimorphism at the growth hormone axis has been demonstrated in MSG-treated rodents. The identification of gender dimorphism in cardiac nutrigenomics may provide the basis for gender-specific medicine in the future. We used microarray analysis to examine changes in cardiac gene transcription in response to TFA and/or MSG feeding in male and female C57Bl/6J mice. Our study animals were bred from female C57Bl/6J mice fed a standard chow diet until 6 weeks of age whereupon they were placed on one of 4 different dietary regimens for a period of 3 weeks prior to mating. The four dietary regimens used in this study were: [1] Standard Chow (Control diet) with ad lib drinking water. [2] Standard Chow, with ad lib drinking water containing 0.64 g/L Monosodium Glutamate (MSG diet). [3] Trans fat diet of 20% (w/w) Partially Hydrogenated Vegetable Shortening containing 8.68% w/w Trans fatty acids(TFA diet). [4] Trans fat Diet #5C4M together with ad lib drinking water containing 0.64 g/L Monosodium Glutamate (TFA+MSG diet). Following mating, the 4 groups of dams were maintained on their respective diets throughout the gestation and nursing period. Male and female offspring used in the following experiments were weighed, weaned onto the same diets and maintained on their respective dietary regimens until they reached 32 weeks of age.Cardiac tissues (8 per diet group) were used at 32 weeks for RNA extraction and hybridization on Affymetrix microarrays.

2011-12-31 | E-GEOD-22881 | biostudies-arrayexpress

Portunus trituberculatus sarcoplasmic calcium binding protein

Project description:P. trituberculatus SCP

| PRJEB82933 | ENA

RNA Encoded Peptide Barcodes Enable Efficient in vivo Screening of RNA Delivery Systems

Project description:LNPs have been demonstrated to hold great promise for the clinical advancement of RNA therapeutics. Continued exploration of LNPs for application in new disease areas requires identification and optimisation of leads in a high throughput way. Currently available high throughput in vivo screening platforms are well suited to screen for cellular uptake but less so for functional cargo delivery. We report on a platform which measures functional delivery of LNPs using unique peptide ‘barcodes’. We describe the design and selection of the peptide barcodes and the evaluation of these for the screening of LNPs. We show that proteomic analysis of peptide barcodes correlates with quantification and efficacy of barcoded reporter proteins both in vitro and in vivo and, that the ranking of selected LNPs using peptide barcodes in a pool correlates with ranking using alternative methods in groups of animals treated with individual LNPs. We show that this system is sensitive, selective, and capable of reducing the size of an in vivo study by screening up to 10 unique formulations in a single pool, thus accelerating the discovery of new technologies for mRNA delivery.

2024-10-17 | PXD053797 | Pride

Nanoparticle stereochemistry-dependent endocytosis improves in vivo mRNA delivery

Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of lipid nanoparticles (LNPs) carrying mRNA in murine liver non parenchymal cells. We report that LNPs containing stereopure 20α-hydroxycholesterol (20α) deliver mRNA to these cells up to three-fold more efficiently than LNPs containing both 20α- and 20ß- hydroxycholesterols (20mix). We show from the sequencing data that 20mix LNPs were sorted into phagocytic pathways, resulting in different functional delivery between stereopure and non-stereopure LNPs. We performed scRNA-seq using the 10X Chromium System, loading ~2,000 cells per condition, and processed the resulting data using Cell Ranger, resulting in an average read depth of ~100,000 reads per cell. These data suggest that stereochemistry-dependent interactions between LNPs and target cells can be exploited to improve mRNA delivery.

2021-08-04 | GSE181333 | GEO

Human brain LC-MS/MS - Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis

Project description:Citrullination as a post-translational modification has been described in a couple of autoimmune diseases like rheumatoid arthritis (RA) and multiples sclerosis (MS). We investigated citrullination brain tissue from MS patients and healthy individuals (HD). The myelin sheath proteins have been the focus of citrullination and neurodegenerative diseases like Alzheimers Disease (AD), Parkinsons and MS. We analysed whole brain tissue of MS patients and HD and established a catalogue of citrullinated proteins. Besides new citrullinated proteins we found additional citrullinated sites on the already described proteins: MBP, GFAP and Vimentin.

2019-04-10 | PXD008344 | Pride

Analysis of corona proteins adsorbing to Cas9 ribonucleoprotein-loaded lipid nanoparticles

Project description:Perotein corona is formed surrouding interface of nanopsrticles upon administered in biological fluids. The quality of protein corona is recognized as the crucial factor for in vivo fate of the administered nanoparticles. In this project, Cas9 ribnonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) capable of robust gene knockout of hepatic genes of interest after single intravenous injection were developed. Compared with short interfering RNA (siRNA)-loaded LNPs, RNP-loaded LNPs showed different morphology, biodistribution, and mechanism of hepatic acccumulation. Therefore, proteome analysis of the corona proteins on the RNP and siRNA-loaded LNPs were performed to elucidate the impact of payloads on nano-bio interactions.

2024-09-05 | PXD055572 | JPOST Repository

Gene expression profiling of effect of Yap inhibition in a genetically engineered mouse model of hepatocellular carcinoma

Project description:Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. We show that YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model (mice with liver-specific Mst1/Mst2 double knockout). Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach. Mice with liver-specific Mst1/Mst2 double-knockout (Adeno-Cre injected Mst1-/-; Mst2Flox/Flox mice) were monitored for the formation of HCC by ultrasound imaging. Animals were then randomized to be treated by intravenous injection of either siYap-LNPs or siLuciferase-LNPs for a period of 9 days.

2015-03-07 | E-GEOD-65665 | biostudies-arrayexpress

Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in failing murine heart

Project description:Advancements of cross-linking mass spectrometry (XL-MS) for structural analysis of proteins bridges the gap between purified systems and native tissue environments. Here, we utilize isobaric quantitative protein interaction reporter technology (iqPIR) to further extend XL-MS to the first system-wide comparative study of mitochondrial proteins from healthy and diseased murine hearts. The failing heart interactome includes 544 statistically significant cross-linked peptide pairs altered in disease condition. Structural insight into ketone oxidation metabolons, OXPHOS machinery, and nucleotide transporter hybrid-conformations, support mitochondrial remodeling in failing heart while bringing forth new hypotheses for pathological mechanisms. Application of quantitative cross-linking technology in live tissue provides molecular-level insight to complex biological systems difficult to model in cell culture, thus providing a valuable resource for study of human diseases.

2022-08-02 | PXD027757 | Pride

Interrogation of RNA-bound proteome with XRNAX illuminates molecular alterations in the mouse brain affected with dysmyelination

Project description:We applied RNA-protein interactome capture method called XRNAX to shed light on RNA-bound proteome in the brain affected with dysmyelination. We found that sets of canonical RBPs that are known to regulate alternative splicing and being engaged in the formation of cytoplasmic granules are perturbed at the level of their RNA interactome in the mouse brain with the inborn deficit of myelin. This dataset contains the whole brain proteomics data as well as LC-MS/MS data from XRNAX extracts enriched in brain RBPs following UV crosslink of RNA-protein interaction in the brain tissue homogenates from wildtype C57BL6/N (experiments 1 and 2) and shiverer mouse model (experiment 3). Whole brain tissues were homogenized using two different methods: biopulverization of the flash-frozen tissue in liquid nitrogen (experiments 2 and 3), and alternatively, tissues submersed in PBS buffer immediately after dissections were disintegrated with Dounce homogenizer (experiment 1).

2024-11-08 | PXD052011 | Pride

Transcription profiling of the Antarctic springtail Cryptopygus antarcticus to investigate cold hardening processes.

Project description:High group animals with supercooling point (SCP) above -15°C and selected low group animals with SCP below -15°C were prepared from Cryptopygus antarcticus collected from wet moss (Sanionia uncinata (Hedw.)) during the austral summer of 2005 at the British Antarctic Survey's research station at Rothera Point, Adelaide Island (67'34'S, 66'8'W).

2008-09-01 | E-MEXP-1569 | biostudies-arrayexpress