# The contribution of skeletal muscle interstitial cells to myogenesis

**Authors:** Fayez Issa, Frédéric Relaix, Joana Esteves de Lima

PMC · DOI: 10.1186/s13395-026-00414-9 · Skeletal Muscle · 2026-01-21

## TL;DR

This review discusses how muscle connective tissue cells contribute to muscle growth and repair by becoming muscle cells.

## Contribution

The paper highlights new evidence that interstitial cells directly contribute to myogenesis, challenging previous assumptions.

## Key findings

- Subpopulations of muscle interstitial cells contribute to myogenesis during development and regeneration.
- Interstitial cells fuse with myofibers in postnatal growth and repair processes.
- Recent studies show the importance of investigating interstitial cell mechanisms in muscle physiology and disease.

## Abstract

The developmental origin of skeletal muscle cell lineages has been extensively studied in the last 50 years. PAX3 + /PAX7 + myogenic progenitors are the foundation for skeletal muscle development and give rise to muscle satellite cells that support skeletal muscle postnatal growth, homeostasis and regeneration. Research into muscle connective tissue interstitial cells established their supportive role in muscle patterning during development and regeneration. With recent advances in mouse genetic lineage tracing, single cell transcriptomics and specific antibodies, the origin and the contribution of non-myogenic interstitial populations to the myogenic lineage have been reexamined. Growing evidence suggests that subpopulations of muscle interstitial cells actively contribute to myogenesis and fuse with myofibers during development, postnatal growth, and regeneration. In this review, we focus on the recent research advances that highlighted the direct contribution of interstitial cells, particularly connective tissue cells, to skeletal muscle growth and repair. We stress the importance of further investigating the mechanisms by which interstitial cells contribute to a myogenic fate in both physiological and pathological conditions.

## Linked entities

- **Genes:** PAX3 (paired box 3) [NCBI Gene 5077], PAX7 (paired box 7) [NCBI Gene 5081]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, Hoxa11 (homeobox A11) [NCBI Gene 15396] {aka Hox-1.9, Hoxa-11}, NES (nestin) [NCBI Gene 10763] {aka Nbla00170}, PAX3 (paired box 3) [NCBI Gene 5077] {aka CDHS, HUP2, PAX-3, WS1, WS3}, Col1a1 (collagen, type I, alpha 1) [NCBI Gene 12842] {aka Col1a-1, Cola-1, Cola1, Mov-13, Mov13}, ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429] {aka ABC15, ABCP, BCRP, BMDP, CD338, CDw338}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, Peg3 (paternally expressed 3) [NCBI Gene 18616] {aka ASF-1, End4, Gcap4, Pw1, Zfp102, mKIAA0287}, Postn (periostin, osteoblast specific factor) [NCBI Gene 50706] {aka A630052E07Rik, OSF-2, Osf2, PLF, PN}, 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}, Myog (myogenin) [NCBI Gene 17928] {aka MYF4, bHLHc3, myo}, Osr1 (odd-skipped related transcription factor 1) [NCBI Gene 23967] {aka Odd1, Osr}, Pdgfrb (platelet derived growth factor receptor, beta polypeptide) [NCBI Gene 18596] {aka CD140b, PDGFR-1, Pdgfr}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, Wnt7a (wingless-type MMTV integration site family, member 7A) [NCBI Gene 22421] {aka Wnt-7a, px, tw}, Pdgfb (platelet derived growth factor subunit B) [NCBI Gene 18591] {aka PDGF-2, PDGF-B, Sis, c-sis}, Itga7 (integrin alpha 7) [NCBI Gene 16404] {aka [a]7, alpha7}, Alpl (alkaline phosphatase, liver/bone/kidney) [NCBI Gene 11647] {aka ALP, APTNAP, Akp-2, Akp2, TNAP, TNSALP}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, Cspg4 (chondroitin sulfate proteoglycan 4) [NCBI Gene 121021] {aka 4732461B14Rik, AN2, Cspg4a, NG2}, Ly6a (lymphocyte antigen 6 family member A) [NCBI Gene 110454] {aka Ly-6A.2, Ly-6A/E, Ly-6E.1, Sca-1, Sca1, TAP}, PEG3 (paternally expressed 3) [NCBI Gene 5178] {aka PW1, ZKSCAN22, ZNF904, ZSCAN24}, CCN4 (cellular communication network factor 4) [NCBI Gene 8840] {aka WISP1, WISP1-OT1, WISP1-UT1, WISP1c, WISP1i, WISP1tc}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, Hoxa7 (homeobox A7) [NCBI Gene 15404] {aka Hox-1.1, M6}, Myh7 (myosin, heavy polypeptide 7, cardiac muscle, beta) [NCBI Gene 140781] {aka B-MHC, MYH-beta/slow, MyHC-I, Myhc-b, Myhcb, beta-MHC}, Pax7 (paired box 7) [NCBI Gene 18509] {aka Pax-7}, Pdgfra (platelet derived growth factor receptor, alpha polypeptide) [NCBI Gene 18595] {aka CD140a, Pdgfr-2}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, PAX7 (paired box 7) [NCBI Gene 5081] {aka CMYO19, CMYP19, HUP1, MYOSCO, PAX7B, RMS2}, MYF6 (myogenic factor 6) [NCBI Gene 4618] {aka CNM3, MRF4, bHLHc4, myf-6}, TWIST2 (twist family bHLH transcription factor 2) [NCBI Gene 117581] {aka AMS, BBRSAY, DERMO1, FFDD3, SETLSS, bHLHa39}, Myh4 (myosin, heavy polypeptide 4, skeletal muscle) [NCBI Gene 17884] {aka MHC2B, MM, MYH-2B, Minimsc, Minmus, MyHC-IIb}, BGN (biglycan) [NCBI Gene 633] {aka DSPG1, MRLS, PG-S1, PGI, SEMDX, SLRR1A}, Loxl3 (lysyl oxidase-like 3) [NCBI Gene 16950] {aka Lor2, Loxl2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, Myh3 (myosin, heavy polypeptide 3, skeletal muscle, embryonic) [NCBI Gene 17883] {aka MyHC-emb, Myhs-e, Myhse}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, HOXA11 (homeobox A11) [NCBI Gene 3207] {aka HOX1, HOX1I, RUSAT1}, TCF7L2 (transcription factor 7 like 2) [NCBI Gene 6934] {aka TCF-4, TCF4}, Twist2 (twist basic helix-loop-helix transcription factor 2) [NCBI Gene 13345] {aka Dermo1, bHLHa39}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Scx (scleraxis scleraxis bHLH transcription factor) [NCBI Gene 20289] {aka Bhlha41, Scl}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, Myf5 (myogenic factor 5) [NCBI Gene 17877] {aka B130010J22Rik, Myf-5, bHLHc2}, SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, Mcam (melanoma cell adhesion molecule) [NCBI Gene 84004] {aka 1-gicerin, CD146, CD149, Muc18, s-endo, s-gicerin}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, FBN1 (fibrillin 1) [NCBI Gene 2200] {aka ACMICD, ECTOL1, FBN, GPHYSD2, MASS, MFLS}, Tnc (tenascin C) [NCBI Gene 21923] {aka C130033P17Rik, Hxb, TN, TN-C, Ten, cytotactin}, Tcf4 (transcription factor 4) [NCBI Gene 21413] {aka 5730422P05Rik, ASP-I2, E2-2, E2.2, ITF-2, ITF-2b}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP}
- **Diseases:** muscle degeneration (MESH:D009410), Myopathies (MESH:D009135), neuromuscular disease (MESH:D009468), muscle hypertrophy (MESH:C536106), immunodeficient (MESH:D007153), hypertrophy (MESH:D006984), type IIb fiber atrophy (MESH:D006938), heterotopic ossification (MESH:D009999), DMD (MESH:D020388), FAPs (MESH:D009810), fibrosis (MESH:D005355), inflammation (MESH:D007249), injury (MESH:D014947), atrophy (MESH:D001284), AFM (MESH:C000629404)
- **Chemicals:** tamoxifen (MESH:D013629)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Coturnix coturnix (Common quail, species) [taxon 9091], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12952177/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12952177/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12952177/full.md

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Source: https://tomesphere.com/paper/PMC12952177