Stange Katja, Röntgen Monika
Working Group Cell Biology of Muscle Growth, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany.
Int J Mol Sci. 2025 Mar 21;26(7):2847. doi: 10.3390/ijms26072847.
Low birth weight (LBW) in various species leads to a pronounced skeletal muscle phenotype and can serve as a model to study muscle formation and draw conclusions for normal and pathological development. We aimed to elucidate in detail how the differentiation of muscular stem cells and their progeny are disturbed in piglets born with LBW. We isolated primary muscle cells from LBW piglets and their normal siblings with two different approaches: (1) single cells from two functionally divergent subpopulations (previously named "fast" and "slow") and (2) cells derived from isolated, intact myofibers. Subsequently, we analyzed their proliferative and differentiative capacity by determining proliferation rate, migration behavior, myotube formation, and myogenic gene and protein expression. LBW led to a decreased proliferation rate and migration potential in cells from the subpopulation fast group. Cells from LBW piglets were generally able to differentiate, but they formed smaller myotubes with less incorporated nuclei, leading to a diminished fusion rate. Myogenic gene expression was also significantly altered due to pig birth weight. Overall, early postnatal muscle development in LBW was disturbed at several crucial steps involving the establishment of a reserve stem cell pool, movement of cells towards existing myofibers, and the ability to form nascent myofibers.
多种物种的低出生体重（LBW）会导致明显的骨骼肌表型，可作为研究肌肉形成以及推断正常和病理发育情况的模型。我们旨在详细阐明出生时低体重仔猪的肌肉干细胞及其后代的分化是如何受到干扰的。我们采用两种不同方法从低体重仔猪及其正常同胞中分离出原代肌肉细胞：（1）来自两个功能不同亚群（先前称为“快”和“慢”）的单细胞，以及（2）从分离的完整肌纤维中获得的细胞。随后，我们通过测定增殖率、迁移行为、肌管形成以及肌源性基因和蛋白质表达来分析它们的增殖和分化能力。低出生体重导致快速亚群细胞的增殖率和迁移潜力降低。低体重仔猪的细胞通常能够分化，但它们形成的肌管较小，融合的细胞核较少，导致融合率降低。由于仔猪出生体重的原因，肌源性基因表达也发生了显著改变。总体而言，低出生体重仔猪出生后的早期肌肉发育在几个关键步骤受到干扰，这些步骤包括储备干细胞池的建立、细胞向现有肌纤维的移动以及形成新生肌纤维的能力。
