251: MuSCs, laminin-α2 and LAMA2 MD

McGowan TJ et al., Nature Communications, doi:10.1038/s41467-025-65703-1 - 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. Key terms: laminin-α2, muscle stem cells, LAMA2 MD, regeneration, proliferation. 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. Article title:Loss of cell-autonomously secreted laminin-α2 drives muscle stem cell dysfunction in LAMA2-related muscular dystrophy First author:McGowan TJ Journal:Nature Communications, doi:10.1038/s41467-025-65703-1 DOI:10.1038/s41467-025-65703-1 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/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/muscle-stem-laminin-alpha2 QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-01-06. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantively audited the transcript’s coverage of: MuSC expression/secreted laminin-α2; intrinsic MuSC proliferation defects in dyW/dyW mice; transplantation results; MuSC-specific Lama2 knockout; human LAMA2 KO hiPSC model; and downstream signaling/cell-cycle implications.- transcript topics: MuSC activation and Lama2 expression; MuSC secretion and remodeling with laminin-α2; dyW/dyW mouse model: regeneration defects and MuSC proliferation; ex vivo MuSC proliferation assays (EdU, cell cycle); MuSC transplantation experiments and intrinsic vs extrinsic defect; MuSC-specific Lama2 knockout effects on proliferation QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- Activated MuSCs express Lama2 and deposit laminin-α2 into their microenviron...