ArticleNucleic acids research2016
Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 103 citations in OpenAlex.
- Deciphering skeletal muscle development: cellular heterogeneity and molecular regulatory networks from single-cell and spatial transcriptomic perspectives.Frontiers in cell and developmental biology · 2026Review
- Tissue-specific aging-a new paradigm based on transcriptional insights from select model systems and humans.Frontiers in genetics · 2026Review
- From iPSCs to myotubes: Identifying potential biomarkers for human FSHD by single-cell transcriptomics.Clinical and translational medicine · 2025Article
- LMNA R482L mutation causes impairments in C2C12 myoblasts subpopulations, alterations in metabolic reprogramming during differentiation, and oxidative stress.Scientific reports · 2025Article
- QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples.Nucleic acids research · 2025Article
- Single-nucleus RNA sequencing reveals HBV-driven metabolic reprogramming and TIMP1-mediated fibrosis in human-liver-chimeric mice.Frontiers in cellular and infection microbiology · 2025Article
- Identification of sex- and inflammation-associated heterogeneity in the mouse omentum.Frontiers in immunology · 2025Article
- Optimisation of cell fate determination for cultivated muscle differentiation.Communications biology · 2024Article
- Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism.Journal of cachexia, sarcopenia and muscle · 2024Article
- Beyond the bulk: overview and novel insights into the dynamics of muscle satellite cells during muscle regeneration.Inflammation and regeneration · 2024Review
- Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle.BMC genomics · 2024Article
- Advancing skeletal health and disease research with single-cell RNA sequencing.Military Medical Research · 2024Review
- Engineered FSHD mutations results in D4Z4 heterochromatin disruption and feedforward DUX4 network activation.iScience · 2024Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.Toxicology and applied pharmacology · 2023Article
- Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia.bioRxiv : the preprint server for biology · 2023Article
- Dysregulation of murine long noncoding single-cell transcriptome in nonalcoholic steatohepatitis and liver fibrosis.RNA (New York, N.Y.) · 2023Article
- Directionality of developing skeletal muscles is set by mechanical forces.Nature communications · 2023Article
- A protocol for single nucleus RNA-seq from frozen skeletal muscle.Life science alliance · 2023Article
- Metabolism and exercise: the skeletal muscle clock takes centre stage.Nature reviews. Endocrinology · 2023Review
- Single-cell analysis of bovine muscle-derived cell types for cultured meat production.Frontiers in nutrition · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Myoblasts are precursor skeletal muscle cells that differentiate into fused, multinucleated myotubes. Current single-cell microfluidic methods are not optimized for capturing very large, multinucleated cells such as myotubes. To circumvent the problem, we performed single-nucleus transcriptome analysis. Using immortalized human myoblasts, we performed RNA-seq analysis of single cells (scRNA-seq) and single nuclei (snRNA-seq) and found them comparable, with a distinct enrichment for long non-coding RNAs (lncRNAs) in snRNA-seq. We then compared snRNA-seq of myoblasts before and after differentiation. We observed the presence of mononucleated cells (MNCs) that remained unfused and analyzed separately from multi-nucleated myotubes. We found that while the transcriptome profiles of myoblast and myotube nuclei are relatively homogeneous, MNC nuclei exhibited significant heterogeneity, with the majority of them adopting a distinct mesenchymal state. Primary transcripts for microRNAs (miRNAs) that participate in skeletal muscle differentiation were among the most differentially expressed lncRNAs, which we validated using NanoString. Our study demonstrates that snRNA-seq provides reliable transcriptome quantification for cells that are otherwise not amenable to current single-cell platforms. Our results further indicate that snRNA-seq has unique advantage in capturing nucleus-enriched lncRNAs and miRNA precursors that are useful in mapping and monitoring differential miRNA expression during cellular differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.