Deep Visual Proteomics defines single-cell identity and heterogeneity

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(8), P. 1231 - 1240

Published: May 19, 2022

Despite the availabilty of imaging-based and mass-spectrometry-based methods for spatial proteomics, a key challenge remains connecting images with single-cell-resolution protein abundance measurements. Here, we introduce Deep Visual Proteomics (DVP), which combines artificial-intelligence-driven image analysis cellular phenotypes automated single-cell or single-nucleus laser microdissection ultra-high-sensitivity mass spectrometry. DVP links to complex subcellular while preserving context. By individually excising nuclei from cell culture, classified distinct states proteomic profiles defined by known uncharacterized proteins. In an archived primary melanoma tissue, identified spatially resolved proteome changes as normal melanocytes transition fully invasive melanoma, revealing pathways that change in manner cancer progresses, such mRNA splicing dysregulation metastatic vertical growth coincides reduced interferon signaling antigen presentation. The ability retain precise information tissue context has implications molecular profiling clinical samples.

Language: Английский

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The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis

Gastroenterology, Journal Year: 2021, Volume and Issue: 162(3), P. 890 - 906

Published: Dec. 7, 2021

Language: Английский

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The universe of galectin-binding partners and their functions in health and disease

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(12), P. 105400 - 105400

Published: Oct. 26, 2023

Galectins, a family of evolutionarily conserved glycan-binding proteins, play key roles in diverse biological processes including tissue repair, adipogenesis, immune cell homeostasis, angiogenesis, and pathogen recognition. Dysregulation galectins their ligands has been observed wide range pathologic conditions cancer, autoimmune inflammation, infection, fibrosis, metabolic disorders. Through protein-glycan or protein-protein interactions, these endogenous lectins can shape the initiation, perpetuation, resolution processes, suggesting potential disease monitoring treatment. However, despite considerable progress, full understanding biology therapeutic not reached due to diversity, multiplicity targets, receptor promiscuity. In this article, we discuss multiple galectin-binding partners present different types, focusing on contributions selected physiologic settings. Understanding molecular bases galectin-ligand particularly glycan-dependency, biochemical nature receptors, underlying signaling events, might contribute designing rational strategies control broad conditions.

Language: Английский

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The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 26, 2024

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including self-renewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into clinic has frequently met with inconsistent outcomes. One suspected reasons this issue is inherent extensive variability that exists among such ATMPs, which makes interpretation efficacy difficult assess, as well compare results various studies. This stems from differences in tissue sources, donor attributes, variances manufacturing protocols, modes administration. MSCs can be isolated tissues bone marrow, umbilical cord, adipose others, each its phenotypic functional characteristics. While different sources do share common features, they also exhibit distinct gene expression profiles properites. Donor-specific factors age, sex, body mass index, underlying health conditions influence MSC phenotype, morphology, differentiation function. Moreover, variations preparation products introduces additional heterogeneity result cell culture media composition, presence or absence added growth factors, use serum supplements culturing techniques. Once are formulated, storage protocols play pivotal role efficacy. Factors affect viability include concentration, delivery solution importantly, post-thawing where applicable. Ensuing, administration critically distribution functionallity administered cells. As therapies continue advance through trials, implication strategies reduce product imperative. Central addressing these challenges need precise prediction responses, require well-defined populations harmonized assessment specific functions. By issues by meaningful approaches, as, e.g., pooling, field overcome barriers towards more consistent effective therapies.

Language: Английский

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Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 15, 2024

Mesenchymal stem/stromal cells (MSCs) represent a heterogeneous cell population distributed throughout various tissues, demonstrating remarkable adaptability to microenvironmental cues and holding immense promise for disease treatment. However, the inherent diversity within MSCs often leads variability in therapeutic outcomes, posing challenges clinical applications. To address this heterogeneity, purification of MSC subpopulations through marker-based isolation has emerged as promising approach ensure consistent efficacy. In review, we discussed reported markers MSCs, encompassing those developed candidate marker strategies high-throughput approaches, with aim explore viable addressing heterogeneity illuminate prospective research directions field.

Language: Английский

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An Integrated Microfluidic‐SERS Platform Enables Sensitive Phenotyping of Serum Extracellular Vesicles in Early Stage Melanomas

Advanced Functional Materials, Journal Year: 2021, Volume and Issue: 32(3)

Published: July 26, 2021

Abstract Precise detection of early melanomas is essential as the stage disease guides treatment options. One growing field that may facilitate advancement melanoma detection, achieved through profiling serum extracellular vesicles (EVs) using sensitive nanotechnology. As a proof principle, platform combines microfluidic device and surface‐enhanced Raman spectroscopy (SERS), expression profiles 4 protein biomarkers in EVs (termed “EV SERS signatures”) derived from 20 patients (including situ melanoma) 21 healthy participants are multiplexed. Significantly higher signal intensities selected observed compared with participants, mean fold‐changes ranging 3.7 to 4.2. It demonstrated EV signatures can accurately separate individuals, an area under curve 0.95. Thus, further development, this ultra‐sensitive platform, combined panel melanoma‐associated biomarkers, has ability differentiate participants.

Language: Английский

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Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1450 - 1450

Published: June 9, 2021

Metastatic melanoma is the most aggressive and difficult to treat type of skin cancer, with a survival rate less than 10%. has conventionally been considered very treat; however, recent progress in understanding cellular molecular mechanisms involved tumorigenesis, metastasis immune escape have led introduction new therapies. These include targeted therapy novel immune-based approaches such as checkpoint blockade (ICB), tumor-infiltrating lymphocytes (TILs), genetically engineered T-lymphocytes chimeric antigen receptor (CAR) T cells. Among these, CAR cell recently made promising strides towards treatment advanced hematological solid cancers. Although might offer hope for patients, it not without its shortcomings, which off-target toxicity, emergence resistance (e.g., due loss), leading eventual relapse. The present review will only describe basic steps metastasis, but also discuss how cells could metastatic melanoma. We outline specific strategies including combination that be used overcome some limitations

Language: Английский

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Mesenchymal Stem Cells

Springer eBooks, Journal Year: 2022, Volume and Issue: unknown, P. 1 - 37

Published: Jan. 1, 2022

Language: Английский

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CD146+CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 8, 2024

Abstract Heterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved endometrial have yet to be elucidated. We aimed explore potential of heterogeneous CAFs promoting The presence melanoma cell adhesion molecule (MCAM; CD146) positive was confirmed by tissue multi-immunofluorescence (mIF), fluorescence activated sorting (FACS). were determined wound healing assays, tuber formation assays cord assays. effects CD146 + on cells studied vitro vivo. expression level interleukin 10 (IL-10) measured quantitative real time polymerase chain reaction (qRT-PCR), western boltting enzyme linked immunosorbent (ELISAs). In addition, transcription factor STAT3 identified bioinformatics methods chromatin immunoprecipitation (ChIP). A subtype marked with found correlated poor prognosis. promoted angiogenesis vasculogenic mimicry (VM) vitro. xenograft tumour model also showed that can facilitate IL-10 elevated CAFs. epithelial-endothelial transformation (EET) further VM via janus kinase 1/signal transducer activator 3 (JAK1/STAT3) signalling pathway. This process could blocked JAK1/STAT3 inhibitor niclosamide. Mechanically, bind promoter cadherin5 (CDH5) promote its which may stimulated IL-10. concluded IL-10/JAK1/STAT3 These findings lead identification targets for antiangiogenic therapeutic strategies cancers.

Language: Английский

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Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116783 - 116783

Published: May 25, 2024

During tumor development, the itself must continuously generate new blood vessels to meet their growth needs while also allowing for invasion and metastasis. One of most common features tumors is hypoxia, which drives process angiogenesis by regulating microenvironment, thus adversely affecting prognosis patients. In addition, overcome unsuitable environments growth, such as nutrient deficiency, hyperacidity, immunosuppression, microenvironment (TME) coordinates in several ways restore supply oxygen nutrients remove metabolic wastes. A growing body research suggests that hypoxia interact through a complex interplay crosstalk, inextricably linked TME. Here, we review TME's positive contribution from an angiogenesis-centric perspective considering objective impact hypoxic phenotypes status limitations current angiogenic therapies.

Language: Английский

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