️ Episode 251: MuSCs, laminin-α2 and LAMA2 MD
In this episode of PaperCast Base by Base, we explore Activated muscle stem cells express and secrete laminin-α2 to remodel their niche, and loss of MuSC-derived laminin-α2 slows MuSC proliferation and delays regeneration in mouse models and human iPSC-derived precursors
Study Highlights:Activated MuSCs upregulate Lama2 and deposit laminin-α2 around proliferating cells during early regeneration. MuSCs from Lama2-deficient dyW/dyW mice progress more slowly through S phase, accumulate in G1, and show reduced expansion ex vivo and in vivo. Transplantation of dyW/dyW MuSCs into wild-type muscle does not restore their proliferative capacity, indicating a cell-intrinsic defect. A MuSC-specific Lama2 knockout recapitulates the slower proliferation and reduces early injury-associated laminin-α2, delaying muscle repair. Isogenic human LAMA2 knockout myogenic precursors also incorporate less EdU and show transcriptional changes consistent with impaired cell-cycle progression.
Conclusion:Self-secreted laminin-α2 is required cell-autonomously for efficient MuSC proliferation and timely muscle regeneration, implicating MuSC dysfunction as a contributor to LAMA2-related muscular dystrophy pathology
Music:Enjoy the music based on this article at the end of the episode.
Reference:McGowan TJ, Reinhard JR, Lewerenz N, Białobrzeska M, Lin S, Stępniewski J, Szade K, Dulak J & Rüegg MA. Loss of cell-autonomously secreted laminin-α2 drives muscle stem cell dysfunction in LAMA2-related muscular dystrophy. Nature Communications (2025) 16:10674. https://doi.org/10.1038/s41467-025-65703-1
License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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Episode link: https://basebybase.castos.com/episodes/muscle-stem-laminin-alpha2
Episode Slug: muscle-stem-laminin-alpha2
Keywords: laminin-α2, muscle stem cells, LAMA2 MD, regeneration, proliferation

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