Skeletal Muscle Nuclei in Mice are not Post-mitotic.

Skeletal Muscle Nuclei in Mice are not Post-mitotic.
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DOI:
10.1093/function/zqac059
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发表时间:
2023
期刊:
Function (Oxford, England)
影响因子:
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其他
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骨骼肌研究领域普遍认为骨骼肌纤维中的细胞核(即肌核)是有丝分裂后不能增殖的。由于我们的氧化氘(D2 O)标记的研究表明,骨骼肌组织中的DNA合成,我们假设,居民肌细胞核可以在体内复制。为了检验这一假设,我们使用了一种小鼠模型,在正常笼活动、功能过载和卫星细胞消融期间,先用GFP暂时标记肌核,然后用D2 O标记。在正常笼活动期间,我们观察到7/7个跖肌(PLA)、6/6个胫骨前肌(TA)、5/7个腓肠肌(GAST)和7/7个四头肌(QUAD)中氘富集到肌细胞DNA中。肌细胞核DNA的平均合成分数(FSR)分别为:PLA为0.0202 ± 0.0093,TA为0.0239 ± 0.0040,TA为0.0076 ± 0.0077。在GAST中为0.0058,在QUAD中为0.0138 ± 0.0039,而在EDL中没有复制。这些FSR值在很大程度上再现在过载和卫星细胞消融条件下,虽然有较高的合成率在过载的PLA肌肉。我们进一步提供了证据,myocytes复制是通过内复制,这导致多倍体。这些新的发现与骨骼肌细胞核是有丝分裂后的教条相矛盾,并为利用肌细胞核的内在复制能力进行肌肉维持和生长开辟了潜在的途径。
The skeletal muscle research field generally accepts that nuclei in skeletal muscle fibers (ie, myonuclei) are post-mitotic and unable to proliferate. Because our deuterium oxide (D2O) labeling studies showed DNA synthesis in skeletal muscle tissue, we hypothesized that resident myonuclei can replicate in vivo. To test this hypothesis, we used a mouse model that temporally labeled myonuclei with GFP followed by D2O labeling during normal cage activity, functional overload, and with satellite cell ablation. During normal cage activity, we observed deuterium enrichment into myonuclear DNA in 7 out of 7 plantaris (PLA), 6 out of 6 tibialis anterior (TA), 5 out of 7 gastrocnemius (GAST), and 7 out of 7 quadriceps (QUAD). The average fractional synthesis rates (FSR) of DNA in myonuclei were: 0.0202 ± 0.0093 in PLA, 0.0239 ± 0.0040 in TA, 0.0076 ± 0. 0058 in GAST, and 0.0138 ± 0.0039 in QUAD, while there was no replication in myonuclei from EDL. These FSR values were largely reproduced in the overload and satellite cell ablation conditions, although there were higher synthesis rates in the overloaded PLA muscle. We further provided evidence that myonuclear replication is through endoreplication, which results in polyploidy. These novel findings contradict the dogma that skeletal muscle nuclei are post-mitotic and open potential avenues to harness the intrinsic replicative ability of myonuclei for muscle maintenance and growth.
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