Muscle samples were obtained from elderly patients with lumbar degenerative disease, and the influence of limited sample size

The gap

Evidence profile

Sourced from the limitations section and future work of the source papers, classified as general, spanning 3 journals.

Supporting evidence — 3 representative gaps

• Single‐Nucleus Atlas of Spinal Sarcopenia Patients Reveals Disruption of Quiescent and Regenerative Satellite Cell Niches in Fatty‐Infiltrated Muscle (2026) · Advanced Science · doi

  muscle samples were obtained from elderly patients with lumbar degenerative disease, and the influence of limited sample size and age-related comorbidities cannot be excluded - snRNA-seq primarily captures nuclear transcripts, ligand-receptor interactions inferred from transcriptomic analyses may not fully reflect actual protein secretion levels or ligand bioavailability - in vivo validation and confirmation across different skeletal muscles remain lacking - the absence of muscle single-cell RNA sequencing data limited our ability to comprehensively characterize immune and inflammatory cell dynamics

  generallimitations section
  Keywords: muscle samples were obtained elderly patients lumbar degenerative
• Transcriptomic advances in studies of muscle stem cell aging: From bulk to single-cell and beyond (2026) · Cell Research · doi

  Transcriptomic advances in studies of muscle stem cell aging: From bulk to single-cell and beyond , Seung Pil Pack1 and Thomas A. Rando2,3 ✉ Soochi Kim 1 ✉ © The Author(s) 2026 Advances in transcriptomic technologies have progressively transformed the questions we can ask and answer about muscle stem cells (MuSCs) during aging. Early microarray and bulk RNA sequencing studies established foundational population-level signatures of aged MuSCs, including attenuation of myogenic and metabolic programs as well as induction of inflammatory and stress- associated transcription. However, these averaged readouts obscured cell-to-cell variability and rare functional states. The transition to single-cell and single-nucleus RNA sequencing marked a turning point by resolving MuSC heterogeneity and revealing that MuSC aging is not purely stochastic. Instead, aged MuSC pools show reproducible changes in state composition, delayed or altered myogenic lineage progression, and selective vulnerability of specific functional subsets. Emerging spatial transcriptomic approaches, although still limited by sensitivity and cell-type discrimination in muscle, are beginning to place these MuSC states into their native tissue context, directly linking transcriptional states, niche organization, and age-associated remodeling. In parallel, integrative multi-omic designs that pair transcriptomics with chromatin accessibility and metabolic measurements have strengthened mechanistic connections among age-associated gene programs, epigenetic remodeling, and metabolic state shifts. Finally, computational frameworks — including trajectory inference, dynamic modeling, and machine learning — are increasingly applied to high-dimensional transcriptomic data to predict aging trajectories and identify candidate rejuvenation targets. In this Perspective, we trace the evolution of transcriptomic technologies through the lens of MuSC aging and highlight how increasing resolution has reframed core models of MuSC decline and plasticity. : , ; ) ( 0 9 8 7 6 5 4 3 2 1 Cell Research (2026) 0:1–9; https://doi.org/10.1038/s41422-026-01240-w INTRODUCTION Skeletal muscle regeneration depends on the activity of muscle stem cells (MuSCs), also known as satellite cells, which reside in a lamina of muscle fibers.1–3 quiescent state beneath the basal Upon injury or stress, MuSCs activate, proliferate, and differentiate to repair damaged tissue while maintaining the stem cell pool through self-renewal.4,5 With aging, however, this tightly regu- lated balance becomes disrupted. Aged MuSCs exhibit reduced regenerative capacity, increased susceptibility to senescence, and altered responses to environmental cues.6–8 Understanding the molecular mechanisms that underlie MuSC aging has long been a central challenge in regenerative biology. MuSCs have served as a model system for the study of stem cell aging,9,10 in part because they can be unequivocally identified in situ and prospectively isolated based on t

  generalfuture workevidence 5/5
  Keywords: cell aging musc muscle muscs transcriptomic stem single cells aged metabolic associated states state advances
• Enhancers integrate microenvironmental signals in muscle stem cells during regeneration in health, disease, and aging (2026) · Skeletal Muscle · doi

  Current research highlights a strong interplay between microenvironmental signaling and the regulation of gene expression during muscle regeneration. While significant progress has been made in defining individual signaling pathways and their downstream targets, the mechanisms by which diverse niche-derived signals are integrated to produce coordinated transcriptional responses remain incompletely understood. In particular, although there is clear evidence that signaling pathways converge on key transcription factors such as MyoD, how these inputs are combined within the broader context of enhancer regulation and chromatin architecture remains to be fully defined. A major challenge moving forward will be to determine how multiple signaling inputs are simultaneously interpreted at specific enhancer elements in vivo. Most current studies examine signaling pathways in isolation or infer convergence through computational analyses, rather than directly testing how combinations of signals influence enhancer activity, chromatin accessibility, and enhancer-promoter interactions. Addressing this question will be critical to understanding how MuSCs generate precise, context-dependent gene expression programs in response to complex niche environments. Advances in multi-omics technologies provide new opportunities to address these questions. Single-cell approaches, including scRNA-seq in combination with computational frameworks such as CellChat and NicheNet, can be used to infer intercellular communication within the niche [137,138]. In parallel, multimodal techniques such as TEA-seq and multi- CUT&Tag enable the simultaneous profiling of chromatin accessibility, transcriptional output, and protein-chromatin interactions within the same cells [139,140]. Integration of these approaches with methods that capture three-dimensional genome organization will be particularly important for linking signaling inputs to changes in enhancer landscapes and chromatin architecture. Together, future studies that combine these approaches will be essential for bridging the current gap between niche-derived signaling and enhancer-mediated gene regulation, and for defining how these processes are coordinated to drive effective muscle regeneration.

  generalfuture workevidence 5/5
  Keywords: signaling enhancer chromatin niche current regulation gene pathways inputs within approaches expression muscle regeneration defining

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