Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)
Published: April 11, 2024
Language: Английский
Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: March 16, 2025
InfoMetrics Analytical ChemistryASAPArticle CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookXWeChatLinkedInRedditEmailBlueskyJump toExpandCollapse ReviewMarch 16, 2025Trends in Mass Spectrometry-Based Single-Cell ProteomicsClick to copy article linkArticle link copied!Ximena Sanchez-AvilaXimena Sanchez-AvilaDepartment of Chemistry Biochemistry, Brigham Young University, Provo, Utah 84602, United StatesMore by Ximena Sanchez-AvilaView BiographyRaphaela M. de OliveiraRaphaela OliveiraDepartment Raphaela OliveiraView BiographySiqi HuangSiqi HuangDepartment Siqi HuangView BiographyChao WangChao WangDepartment Chao WangView Biographyhttps://orcid.org/0009-0008-6197-2985Ryan T. Kelly*Ryan KellyDepartment States*Email: [email protected]More Ryan KellyView Biographyhttps://orcid.org/0000-0002-3339-4443Other Access OptionsAnalytical ChemistryCite this: Anal. Chem. 2025, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acs.analchem.5c00661https://doi.org/10.1021/acs.analchem.5c00661Published March 2025 Publication History Received 28 January 2025Accepted February 2025Revised 23 2025Published online 16 2025review-article© American Chemical SocietyRequest reuse permissionsACS Publications© SocietySubjectswhat are subjects Article automatically applied from the ACS Subject Taxonomy describe scientific concepts themes article. Cells Isolation spectrometry Peptides proteins Sample preparation Note: In lieu an abstract, this is article's first page. Read To access article, please review available below. Get instant Purchase for 48 hours. Check out below using your ID or as a guest. Restore my guest Recommended through Your Institution You may have institution. institution does not content. Add change let them know you'd like include access. Through Recommend Name Loading Institutional Login Options... Change Explore subscriptions institutions Log with if you previously purchased it member benefits. hours $48.00 cart Checkout Cited By Click section linkSection copied!This has yet been cited other publications.Download PDF e-AlertsGet e-AlertsAnalytical copied!https://doi.org/10.1021/acs.analchem.5c00661Published 2025© permissionsArticle Views6Altmetric-Citations-Learn about these metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both HTML) across all individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure attention that research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given how calculated.Recommended Articles
Language: Английский
Citations
0
Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)
Published: April 16, 2025
Abstract Background Cytoplasmic aggregation of TAR DNA binding protein 43 (TDP-43) in neurons is one the hallmarks TDP-43 proteinopathy. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are closely associated with proteinopathy; however, it remains uncertain whether initiates pathology or a consequence it. Methods To demonstrate aggregation, we applied optoDroplet technique Caenorhabditis elegans ( C. ), which allows spatiotemporal modulation phase separation assembly. Results We that optogenetically induced aggregates exhibited insolubility similar to observed These increased severity neurodegeneration, particularly GABAergic motor neurons, exacerbated sensorimotor dysfunction . Conclusions present an optogenetic model proteinopathy provides insight into neuropathological mechanisms aggregates. Our serves as promising tool for identifying therapeutic targets
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 25, 2025
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder only limited number risk loci identified. We report our comprehensive genome-wide association study as part International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe Australia, meta-analysis Dementia-seq cohort. confirm UNC13A strongest overall factor identify TNIP1 novel factor. In subgroup analyzes, we further significant specific to each three main pathological subtypes (A, B C), well enrichment distinct tissues, brain regions, subtypes, suggesting disease aetiologies subtypes. Rare variant analysis confirmed TBK1 identified C3AR1, SMG8, VIPR1, RBPJL, L3MBTL1 ANO9, subtype-specific genes, highlighting role innate adaptive immunity notch signaling pathway FTLD-TDP, potential diagnostic therapeutic implications.
Language: Английский
Citations
0
Published: June 11, 2024
Single cell proteomics by mass spectrometry (SCP) is an emerging field of study that has captured the interest and imagination biologists in a wide array disciplines. In pursuit this new dizzying technologies techniques have demonstrated ability to quantify hundreds few thousand proteins single mammalian cells typical size. One striking characteristic these methods range relative costs associated with analysis each cell. We attempted estimate cost per across 17 different studies based on quotes we obtained for hardware, reagents instrument support plans relation number can be analyzed day. Before including labor or facilities, find analyze size from less than <$2 over $50 The increase appears directly related decrease throughput as measured theoretical maximum Perhaps most surprising observation average year. This when compared emergence RNA sequencing where increased, cost/cell decreased exponentially first 7 years field’s emergence. While made many assumptions obtain estimates, hope will informative scientists interested obtaining SCP data spectrometrists who are considering entering field. provided spreadsheet simple calculator supplemental allow others adjust our calculations other variables which inevitably described future.
Language: Английский
Citations
2
Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35342 - e35342
Published: July 29, 2024
Language: Английский
Citations
2
PROTEOMICS, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 16, 2024
ABSTRACT Single‐cell proteomics (SCP) has advanced significantly in recent years, with new tools specifically designed for the preparation and analysis of single cells now commercially available to researchers. The field is sufficiently mature be broadly accessible any lab capable isolating performing bulk‐scale proteomic analyses. In this review, we highlight work SCP that lowered barrier entry, thus providing a practical guide those who are newly entering field. We outline fundamental principles report multiple paths accomplish key steps successful experiment including sample preparation, separation, mass spectrometry data acquisition analysis. recommend researchers start label‐free workflow, as achieving high‐quality quantitatively accurate results more straightforward than label‐based multiplexed strategies. By leveraging these means, can confidently perform experiments make meaningful discoveries at single‐cell level.
Language: Английский
Citations
2
Journal of Proteome Research, Journal Year: 2024, Volume and Issue: unknown
Published: July 9, 2024
Single-cell analysis is an active area of research in many fields biology. Measurements at single-cell resolution allow researchers to study diverse populations without losing biologically meaningful information sample averages. Many technologies have been used single cells, including mass spectrometry-based proteomics (SCP). SCP has seen a lot growth over the past couple years through improvements data acquisition and analysis, leading greater proteomic depth. Because method development main focus SCP, biological applications sprinkled only as proof-of-concept. However, methods now provide significant coverage proteome implemented laboratories. Thus, primary question address our community whether current state technology ready for widespread adoption inquiry. In this Perspective, we examine potential three thematic areas investigation: cell annotation, developmental trajectories, spatial mapping. We identify that limitation throughput. As depth target date, advocate change facilitate measuring tens thousands proteomes enable beyond
Language: Английский
Citations
1
Small Methods, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 29, 2024
Abstract Low‐input proteomics, also referred to as micro‐ or nanoproteomics, has become increasingly popular it allows one elucidate molecular processes in rare biological materials. A major prerequisite for the analytics of minute protein amounts, e.g., derived from low cell numbers, down single cells, is availability efficient sample preparation methods. Digital microfluidics (DMF), a technology allowing handling and manipulation liquid volumes, recently been shown be powerful versatile tool address challenges low‐input proteomics. Here, an overview provided on recent advances proteomics using DMF. In particular, capability DMF isolate proteomes cells small model organisms, perform all necessary chemical steps, such denaturation proteolytic digestion on‐chip, are highlighted. Additionally, prerequisites making these steps compatible with follow‐up analytical methods chromatography‐mass spectrometry will discussed.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 24, 2024
ABSTRACT Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive degeneration of motor neurons in cerebral cortex and spinal cord, with rapid progression from diagnosis to death. The great majority ALS cases around 50% FTD present TDP-43 pathology, leading mislocalization cytoplasmic aggregation TDP-43, which can result both its loss nuclear functions gain toxicity cytoplasm. other RNA-binding proteins accumulate stress granules (SGs) under conditions. ubiquitin-specific protease 10 (USP10) an inhibitor SGs assembly that has been recently linked neurodegeneration. Here, we identified new functional interaction between USP10, USP10 control multiple aspects biology are thought play important roles involvement disease pathogenesis, such as aggregation, expression splicing functionality. In turn, also able diverse biology, levels, function. Critically, found dysregulation patients, overall suggesting possible role for ALS/FTD pathogenesis.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 23, 2024
Abstract Cytoplasmic accumulation and aggregation of TDP-43 is a hallmark ∼97% ALS cases. Formation insoluble aggregates suggested to either directly or indirectly cause motor neuron loss progressive neuromuscular degeneration, although how this occurs not precisely understood. observed in stress granules (SG). SGs are ribonucleoprotein (RNP) complexes formed during conditions, consisting mRNAs RNA-binding proteins (RNPs). Chronic TDP-43/SG formation may play role degeneration ALS. The composition vivo TDP-43-asscociated known. This knowledge provide insights into the molecular pathways impaired by TDP-43-associated suggest disease modifying mechanisms. aim study was isolate analyse proteome SG fraction from brain tissue end-stage TDP-43ΔNLS mice. Proteomic analysis identified 134 enriched 17 depleted mice, when compared control Bioinformatics analyses impacted preparation that NEFH-TDP-43ΔNLS mice have sustained formation, CLUH granule recruitment mitochondrial metabolism. first time has been demonstrated known suggests cell starvation potential mechanism could be targeted Highlights We present detailed protocol for extraction cross-linked TDP containing tissue. proteomics data an mouse model. identify mRNA transport protein targets trapped brain. Reanalysing axonal soluble supports link between axons. Propose model where metabolic enzymes via dependent results death
Language: Английский
Citations
0