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Multimodal single-cell RNA sequencing enables the precise mapping of transcriptional and phenotypic features of cellular differentiation states but does not allow for simultaneous integration of critical posttranslational modification data. Here, we describe SUrface-protein Glycan And RNA-seq (SUGAR-seq), a method that enables detection and analysis of N-linked glycosylation, extracellular epitopes, and the transcriptome at the single-cell level. Integrated SUGAR-seq and glycoproteome analysis identified tumor-infiltrating T cells with unique surface glycan properties that report their epigenetic and functional state.
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http://dx.doi.org/10.1126/sciadv.abe3610 | DOI Listing |
Adv Sci (Weinh)
September 2025
School of Artificial Intelligence, Jilin University, Changchun, 130012, China.
Single-cell multi-omics technologies are pivotal for deciphering the complexities of biological systems, with Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) emerging as a particularly valuable approach. The dual-modality capability makes CITE-seq particularly advantageous for dissecting cellular heterogeneity and understanding the dynamic interplay between transcriptomic and proteomic landscapes. However, existing computational models for integrating these two modalities often struggle to capture the complex, non-linear interactions between RNA and antibody-derived tags (ADTs), and are computationally intensive.
View Article and Find Full Text PDFStem Cell Reports
August 2025
Neural Stem Cell Institute, 150 New Scotland Ave., Albany, NY 12208, USA.
The retinal pigment epithelium (RPE) is a pigmented monolayer of cells beneath the neural retina that supports photoreceptor cell function essential for vision. Our study explores the diversity of adult human RPE subpopulations and associated implications for retinal biology. Employing cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we identified distinct RPE cell subpopulations characterized by unique single-cell transcriptomic and surface protein signatures.
View Article and Find Full Text PDFAnn Neurol
August 2025
Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Objective: We aimed to investigate disease-related and anti-CD20 therapy-related changes in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients compared to healthy controls (HC) using multi-omics single-cell analysis.
Methods: Targeted single-cell sequencing of transcriptomes and epitopes was performed on PBMCs isolated from 64 blood samples collected from MS patients at baseline and at 3 time points following anti-CD20 treatment, alongside HC. Multicolor spectral flow cytometry was performed on 15 of the samples.
Brief Bioinform
July 2025
Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Ghods 37, Tehran, 1417763135, Iran.
The rapid advancement of single-cell omics technologies such as single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin with high throughput sequencing has transformed our understanding of cellular heterogeneity and regulatory mechanisms. However, integrating these data types remains challenging due to distributional discrepancies and distinct feature spaces. To address this, we present a novel single-cell Contrastive INtegration framework (sCIN) that integrates different omics modalities into a shared low-dimensional latent space.
View Article and Find Full Text PDFCell Rep Med
August 2025
Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria. Electronic address:
Second mitochondrial activator of caspase (SMAC) mimetics (SMACm) and bromodomain and extra-terminal domain (BET) inhibitors (BETi) are two distinct classes of novel anticancer therapeutics. So far, broad clinical benefit for either monotherapy has not been achieved, calling for effective combination strategies. We show that the combination of BI 891065, a monovalent oral SMACm antagonist of inhibitor of apoptosis protein 1 (cellular inhibitor of apoptosis protein 1 [cIAP1]), and BI 894999, a potent and selective oral BETi, significantly impaired cancer cell proliferation irrespective of tissue context.
View Article and Find Full Text PDF