2026-09-14 国立精神・神経医療研究センター
.jpg "筋強直性ジストロフィー1型の筋病理に、 筋幹細胞の融合と筋核の成熟障害が関与することを発見")
【図1】正常筋およびDM1患者筋のH&E染色画像
＜関連情報＞
- https://www.ncnp.go.jp/topics/detail.php?@uid=WVpfYU7IG5m7pp3F
- https://www.nature.com/articles/s41467-026-76476-6
MBNLの枯渇は、筋強直性ジストロフィー1型における幹細胞融合と未成熟な筋核状態を引き起こす MBNL depletion drives stem cell fusion and immature myonuclear states in myotonic dystrophy type 1
Vanessa Todorow,Xavière Lornage,Shinichiro Hayashi,Fiorella Carla Grandi,Zoé Clerc,Jeanne Lainé,Michel Ney,Mégane Lemaitre,Corentin Rouxel,Maria Kondili,Piera Smeriglio,Hanseul Oh,Mie Kato,Nobuyuki Eura,Yoshihiko Saito,Francia Victoria A. De Los Reyes,Satoru Noguchi,Benedikt Schoser,Denis Furling,Ichizo Nishino,Peter Meinke & Frédérique Rau
Nature Communications Published:06 August 2026
DOI:https://doi.org/10.1038/s41467-026-76476-6
Abstract
Myotonic dystrophy type 1 is caused by the expression of expanded CTG repeats in the DMPK gene and the resulting loss of function of MBNL protein. Affected skeletal muscle displays abundant centrally located nuclei despite limited immune-cell–associated fibre necrosis, complicating interpretation of muscle damage and remodelling mechanisms. Here we show that muscle stem cells are activated and fuse with existing muscle fibres in myotonic dystrophy type 1. Single-nucleus transcriptomics in patient’s muscle identifies increased activated muscle stem cells and distinct myonuclear populations exhibiting transitional transcriptional states, including muscle stem cell associated markers and elevated DMPK expression. Myofibre-specific MBNL knockdown mouse models demonstrate that muscle stem cell fusion contributes to central nucleation, whereas their deletion does not improve myotonia or muscle strength. Together, these findings indicate that loss of MBNL function in muscle drives myonuclear accretion through stem cell-mediated fusion, giving rise to myonuclei with immature states in myotonic dystrophy type 1.
