# Across the space: applications of spatial transcriptomic technology in healthy and diseased muscle

**Authors:** Laura Virtanen, Chiara D’Ercole, Lorenzo Giordani

PMC · DOI: 10.3389/fcell.2025.1656918 · Frontiers in Cell and Developmental Biology · 2025-10-21

## TL;DR

Spatial transcriptomics helps understand how cells interact in muscle tissue, both healthy and diseased, by preserving their spatial arrangement.

## Contribution

The paper reviews ST techniques and their impact on understanding muscle regeneration and disease mechanisms.

## Key findings

- ST techniques preserve anatomical information to study cellular interactions in muscle.
- Spatial localization is crucial for understanding muscle regeneration and repair mechanisms.
- ST has enabled recent advancements in studying skeletal muscle dynamics and disease.

## Abstract

In recent years, spatial transcriptomics (ST) has emerged as a groundbreaking technology with the potential to transform and accelerate our understanding of cellular crosstalk. While single-cell approaches have uncovered an unexpected level of cellular heterogeneity in both healthy and diseased tissues, they remain limited in their ability to capture cellular interactions in the native microenvironment. ST techniques bridge this gap by preserving anatomical information, enabling a direct investigation of spatially defined cellular interactions. This feature is particularly relevant in tissues such as skeletal muscle, where syncytial myofibers coexist with a heterogeneous set of interstitial cell populations. Spatial localization is a key factor during muscle regeneration, particularly as stem cell progression is driven by complex interactions between resident and recruited cell populations. Understanding these spatial dynamics is therefore critical to better characterize the fundamental mechanisms of muscle repair and identify aberrant signaling pathways of chronic injury or impaired regeneration. In this review, we will explore the various types of ST techniques, provide a brief summary of the available analytical tools, and highlight recent advancements in the skeletal muscle field enabled by the application of ST.

## Full-text entities

- **Genes:** Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, Osmr (oncostatin M receptor) [NCBI Gene 18414] {aka OSMRB}, MYH3 (myosin heavy chain 3) [NCBI Gene 4621] {aka CPSFS1A, CPSFS1B, CPSKF1A, CPSKF1B, DA2A, DA2B}, Myog (myogenin) [NCBI Gene 17928] {aka MYF4, bHLHc3, myo}, Myl1 (myosin, light polypeptide 1) [NCBI Gene 17901] {aka MLC1f, MLC3f, Mylf}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) [NCBI Gene 3158], Sdc4 (syndecan 4) [NCBI Gene 20971] {aka S4, Synd4, ryudocan, syndecan-4}, Ctsk (cathepsin K) [NCBI Gene 13038] {aka MMS10-Q, Ms10q, catK}, Mdk (midkine) [NCBI Gene 17242] {aka MK, Mek}, Myh1 (myosin, heavy polypeptide 1, skeletal muscle, adult) [NCBI Gene 17879] {aka A530084A17Rik, IId, IId/x, MHC-2X/D, MHC2X/D, MYHC-IIX}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 20750] {aka 2AR, Apl-1, BNSP, BSPI, Bsp, ETA-1}, Myod1 (myogenic differentiation 1) [NCBI Gene 17927] {aka MYF3, MyoD, Myod-1, bHLHc1}, Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}, ITGAX (integrin subunit alpha X) [NCBI Gene 3687] {aka CD11C, SLEB6}, Vim (vimentin) [NCBI Gene 22352], Nucleolin (nucleolin multifunctional protein) [NCBI Gene 17975] {aka B530004O11Rik, C23, D0Nds28, D1Nds28, Ncl, Nucl}, DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, LGR5 (leucine rich repeat containing G protein-coupled receptor 5) [NCBI Gene 8549] {aka FEX, GPR49, GPR67, GRP49, HG38}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, ITGB2 (integrin subunit beta 2) [NCBI Gene 3689] {aka CD18, LAD, LCAMB, LFA-1, MAC-1, MF17}, MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321] {aka HME, ME, MME, MMP-12}, Lrp1 (low density lipoprotein receptor-related protein 1) [NCBI Gene 16971] {aka A2mr, CD91, Lrp, b2b1554Clo}, GATM (glycine amidinotransferase) [NCBI Gene 2628] {aka AGAT, AT, CCDS3, FRTS, FRTS1, RFS}, CARMN (cardiac mesoderm enhancer-associated non-coding RNA) [NCBI Gene 728264] {aka CARMEN, MIR143HG}, Myh4 (myosin, heavy polypeptide 4, skeletal muscle) [NCBI Gene 17884] {aka MHC2B, MM, MYH-2B, Minimsc, Minmus, MyHC-IIb}, Itgb1 (integrin beta 1 (fibronectin receptor beta)) [NCBI Gene 16412] {aka 4633401G24Rik, CD29, Fnrb, Gm9863, gpIIa}, Lgals3 (lectin, galactose binding, soluble 3) [NCBI Gene 16854] {aka GBP, L-34, Mac-2, gal3}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Acadl (acyl-Coenzyme A dehydrogenase, long-chain) [NCBI Gene 11363] {aka LCAD}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD14 (CD14 molecule) [NCBI Gene 929], MEG3 (maternally expressed 3) [NCBI Gene 55384] {aka FP504, GTL2, LINC00023, Lnc-DLK1-35, NCRNA00023, PRO0518}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, Pygm (muscle glycogen phosphorylase) [NCBI Gene 19309] {aka PG}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, MYREM (MYBPC2 cis regulating lncRNA enhancer of myogenesis) [NCBI Gene 128266840] {aka Charme, HSCHARME, lncFAM}, DST (dystonin) [NCBI Gene 667] {aka BP240, BPA, BPAG1, CATX-15, CATX15, CMYO29}, Meg3 (maternally expressed 3) [NCBI Gene 17263] {aka 2900016C05Rik, 3110050O07Rik, 6330408G06Rik, D12Bwg1266e, Gtl2}, Bgn (biglycan) [NCBI Gene 12111] {aka BG, DSPG1, PG-S1, PGI, SLRR1A}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Osm (oncostatin M) [NCBI Gene 18413] {aka OncoM}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}, Col1a2 (collagen, type I, alpha 2) [NCBI Gene 12843] {aka Col1a-2, Cola-2, Cola2, oim}, Dmd (dystrophin, muscular dystrophy) [NCBI Gene 13405] {aka DXSmh7, DXSmh9, Dp427, Dp71, dys, mdx}, POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, Myl3 (myosin, light polypeptide 3) [NCBI Gene 17897] {aka MLC1SB, MLC1s, MLC1v, Mylc, VLC1}, MYBPC2 (myosin binding protein C2) [NCBI Gene 4606] {aka MYBPC, MYBPCF, fsMyBP-C}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Tgfbr2 (transforming growth factor, beta receptor II) [NCBI Gene 21813] {aka 1110020H15Rik, DNIIR, RIIDN, TBR-II, TbetaR-II, TbetaRII}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, Chrne (cholinergic receptor, nicotinic, epsilon polypeptide) [NCBI Gene 11448] {aka AChrepsilon, Acre, nAChRE}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, ACTG2 (actin gamma 2, smooth muscle) [NCBI Gene 72] {aka ACT, ACTA3, ACTE, ACTL3, ACTSG, MMIHS5}, Prg4 (proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)) [NCBI Gene 96875] {aka CACP, DOL54, JCAP, MSF, SZP, lubricin}, MYH6 (myosin heavy chain 6) [NCBI Gene 4624] {aka ASD3, CMD1EE, CMH14, MYHC, MYHCA, SSS3}
- **Diseases:** bladder cancer (MESH:D001749), necrosis (MESH:D009336), type IIA-IIX (MESH:C562844), neuromuscular diseases (MESH:D009468), muscular dystrophies (MESH:D009136), Muscle disorders (MESH:D009135), muscle degeneration (MESH:D009410), MIBC (MESH:D000093284), hypertrophy (MESH:D006984), dystrophy (MESH:D058499), ALS (MESH:D000690), bone demineralization (MESH:D018488), metabolic diseases (MESH:D008659), Becker Muscular Dystrophy (MESH:D020388), HO (MESH:D009999), atrophy (MESH:D001284), calcification (MESH:D002114), tumor (MESH:D009369), impaired mitochondrial functions (MESH:D028361), sciatic nerve compression (MESH:D009408), dystrophic muscle (MESH:D019042), fibrosis (MESH:D005355), Muscle damage (MESH:D009133), inflammation (MESH:D007249), degenerative disorder (MESH:D019636), injuries (MESH:D014947)
- **Chemicals:** calcium (MESH:D002118), Formalin (MESH:D005557), (A) (MESH:D001151), eosin (MESH:D004801), agarose (MESH:D012685), lipid (MESH:D008055), ATP (MESH:D000255), tazemetostat (MESH:C000593333), polyamine (MESH:D011073), fatty acid (MESH:D005227), putrescine (MESH:D011700), hematoxylin (MESH:D006416), formamide (MESH:C031066), Prednisolone (MESH:D011239), H&amp;E (MESH:D006371), CosMX (-), ketone body (MESH:D007657), biotin (MESH:D001710), glycogen (MESH:D006003), tricarboxylic acid (MESH:D014233), deflazacort (MESH:C021988), GSK126 (MESH:C577920), paraffin (MESH:D010232)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797), /2J — Homo sapiens (Human), Transformed cell line (CVCL_N185), BL6 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0157)

## Full text

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## Figures

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## References

133 references — full list in the complete paper: https://tomesphere.com/paper/PMC12583089/full.md

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Source: https://tomesphere.com/paper/PMC12583089