Human iPSC-Derived Mononuclear Phagocytes Improve Cognition and Neural Health across Multiple Mouse Models of Aging and Alzheimer's Disease.

Young blood or plasma improves cognitive function in aged animals but has limited availability. The current study generates a subtype of young blood cells from easily expandable induced pluripotent stem cells and evaluates their effects on age- and Alzheimer's disease (AD)-associated cognitive and neural decline. In aging mice, intravenous delivery of induced mononuclear phagocytes (iMPs) improves performance in hippocampus-dependent cognitive tasks, increases neural health, and reduces neuroinflammation.

Dynamic extracellular interactions with AMPA receptors.

Synaptic plasticity in the central nervous system enables the encoding, storing, and integrating new information. AMPA-type glutamate receptors (AMPARs) are ligand-gated ion channels that mediate most fast excitatory synaptic transmission in the brain, and plasticity of AMPARs signaling underlies the long-lasting changes in synaptic efficacy and strength important for learning and memory. Recent work has indicated that the enigmatic N-terminal domain (NTD) of AMPARs may be a critical regulator of synaptic targeting and plasticity of AMPARs.

Remote blood sampling differential protein expression associated with persistent hypertension following a hypertensive disorder of pregnancy.

Objective: Hypertensive disorders of pregnancy are associated with future cardiovascular risk, however, the underlying mechanisms are unclear. We sought to test the feasibility of postpartum remote blood sampling following a hypertensive disorder of pregnancy and subsequently identify differentially expressed proteins in individuals who developed hypertension.

Study Design: We used data from a randomized clinical trial evaluating the feasibility of lifestyle intervention and home blood pressure monitoring of individuals with pre-pregnancy body mass index ≥25 kg/m and new-onset hypertensive disorders of pregnancy.

Impact of cardiosphere-derived cells on the maladapted right ventricular muscle in a rat sugen/hypoxia model of pulmonary hypertension with right ventricular dysfunction.

Background And Aims: With pulmonary arterial hypertension (PAH), right ventricular (RV) function is a major determinant of survival. Despite current therapies, maladaptive changes ensue in the RV muscle of PAH patients, culminating in RV dysfunction and failure. The aims of the study were to evaluate the impact of intra-coronary (IC) cardiosphere-derived cells (CDCs) in attenuating the maladaptive pathobiology in the RV muscle and evaluating mechanisms underlying improvements in RV function.

High-Throughput Workflow for Detergent-free Cell-Based Proteomic Characterization.

We have developed an automated cell-based workflow for the quantification of proteins by liquid chromatography-mass spectrometry (LC-MS) that facilitates large-scale perturbation studies carried out in a 96-well plate format and enables the preparation of one full plate in approximately 4 h, showcasing a high-throughput (HTP) concept. Cells were grown in a 96-well plate and lysed via ultrasonication. Proteins were subsequently solubilized, extracted, and processed into tryptic peptides for 2 h before being acquired by data-independent acquisition mass spectrometry (DIA-MS).

Toward Real-Time Proteomics: Blood to Biomarker Quantitation in under One Hour.

Multistep multihour tryptic proteolysis has limited the utility of bottom-up proteomics for cases that require immediate quantitative information. The power of proteomics to quantify biomarkers of health status cannot practically assist in clinical care if the dynamics of disease outpaces the turnaround of analysis. The recently available hyperthermoacidic archaeal (HTA) protease "Krakatoa" digests samples in a single 5 to 30 min step at pH 3 and >80 °C in conditions that disrupt most cells and tissues, denature proteins, and block disulfide reformation thereby dramatically expediting and simplifying sample preparation.

Single Cell Proteomics Reveals Novel Cell Phenotypes in Marfan Mouse Aneurysm.

Background: Single-cell omics technology is a powerful tool in biomedical research. However, single cell proteomics has lagged due to an inability to amplify peptides in a similar fashion to nucleotide strings. Single cell proteomics is important because proteins are the main functional unit in cells, and they often poorly correlate with mRNA quantities.

Longitudinal integrated proteomic and metabolomic skin changes in patients with atopic dermatitis treated with dupilumab.

Background: Inhibition of IL-4/IL-13-driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: Our aim was to assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strips (STSs) were collected from lesional/nonlesional skin of 20 patients with AD during a 16-week dupilumab treatment course and from 20 healthy volunteers (HVs) followed for 16 weeks.

Single-Cell Proteomics Reveals Specific Cellular Subtypes in Cardiomyocytes Derived From Human iPSCs and Adult Hearts.

Single-cell proteomics was performed on human induced pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, and adult cardiomyocytes. More than 700 proteins could be simultaneously measured in each cell revealing unique subpopulations. A subset of iPSCs expressed higher levels of Lin28a and Tra-1-60 towards the outer edge of cell colonies.

Differentiation between descending thoracic aortic diseases using machine learning and plasma proteomic signatures.

Background: Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

Methods: This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases.

Protein Coronas on Functionalized Nanoparticles Enable Quantitative and Precise Large-Scale Deep Plasma Proteomics.

Background: The wide dynamic range of circulating proteins coupled with the diversity of proteoforms present in plasma has historically impeded comprehensive and quantitative characterization of the plasma proteome at scale. Automated nanoparticle (NP) protein corona-based proteomics workflows can efficiently compress the dynamic range of protein abundances into a mass spectrometry (MS)-accessible detection range. This enhances the depth and scalability of quantitative MS-based methods, which can elucidate the molecular mechanisms of biological processes, discover new protein biomarkers, and improve comprehensiveness of MS-based diagnostics.

A Complete Workflow for High Throughput Human Single Skeletal Muscle Fiber Proteomics.

Skeletal muscle is a major regulatory tissue of whole-body metabolism and is composed of a diverse mixture of cell (fiber) types. Aging and several diseases differentially affect the various fiber types, and therefore, investigating the changes in the proteome in a fiber-type specific manner is essential. Recent breakthroughs in isolated single muscle fiber proteomics have started to reveal heterogeneity among fibers.

Proteomics of novel induced pluripotent stem cell-derived vascular endothelial cells reveal extensive similarity with an immortalized human endothelial cell line.

The vascular endothelium constitutes the inner lining of the blood vessel, and malfunction and injuries of the endothelium can cause cardiovascular diseases as well as other diseases including stroke, tumor growth, and chronic kidney failure. Generation of effective sources to replace injured endothelial cells (ECs) could have significant clinical impact, and somatic cell sources like peripheral or cord blood cannot credibly supply enough endothelial cell progenitors for multitude of treatments. Pluripotent stem cells are a promising source for a reliable EC supply, which have the potential to restore tissue function and treat vascular diseases.

High-Throughput Single-Cell Proteomic Analysis of Organ-Derived Heterogeneous Cell Populations by Nanoflow Dual-Trap Single-Column Liquid Chromatography.

Identification and proteomic characterization of rare cell types within complex organ-derived cell mixtures is best accomplished by label-free quantitative mass spectrometry. High throughput is required to rapidly survey hundreds to thousands of individual cells to adequately represent rare populations. Here we present parallelized nanoflow dual-trap single-column liquid chromatography (nanoDTSC) operating at 15 min of total run time per cell with peptides quantified over 11.

Complete Workflow for High Throughput Human Single Skeletal Muscle Fiber Proteomics.

Skeletal muscle is a major regulatory tissue of whole-body metabolism and is composed of a diverse mixture of cell (fiber) types. Aging and several diseases differentially affect the various fiber types, and therefore, investigating the changes in the proteome in a fiber-type specific manner is essential. Recent breakthroughs in isolated single muscle fiber proteomics have started to reveal heterogeneity among fibers.

Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency.

Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD).

High Throughput Single Cell Proteomic Analysis of Organ Derived Heterogeneous Cell Populations by Nanoflow Dual Trap Single Column Liquid Chromatography.

Identification and proteomic characterization of rare cell types within complex organ derived cell mixtures is best accomplished by label-free quantitative mass spectrometry. High throughput is required to rapidly survey hundreds to thousands of individual cells to adequately represent rare populations. Here we present parallelized nanoflow dual-trap single-column liquid chromatography (nanoDTSC) operating at 15 minutes of total run time per cell with peptides quantified over 11.