Nuclear numbers in syncytial muscle fibers promote size but limit the development of larger myonuclear domains.
Nuclear numbers in syncytial muscle fibers promote size but limit the development of larger myonuclear domains.
复制标题
DOI：
10.1038/s41467-020-20058-7
复制
发表时间：
2020-12-08
影响因子：
16.6
通讯作者：
Millay DP
中科院分区：
文献类型：
--
作者：
Cramer AAW;Prasad V;Eftestøl E;Song T;Hansson KA;Dugdale HF;Sadayappan S;Ochala J;Gundersen K;Millay DP
哺乳动物细胞在细胞大小上表现出显著的多样性，但是调节这些大小的建立和维持的因素仍然知之甚少。骨骼肌尤其如此，骨骼肌由合胞体肌纤维组成，在发育过程中，每一个合胞体肌纤维都积累了数百个细胞核。在这里，我们直接探讨假设的因果关系，多核和建立正常大小，通过滴定小鼠新生儿发育过程中的肌球蛋白数量。三个独立的小鼠模型，其中肌细胞数量减少了75%，55%或25%，导致发现肌核具有储备能力，以支持发育中的肌纤维中更大的功能性细胞质体积。令人惊讶的是，结果显示，细胞核数量和储备能力之间呈反比关系。我们提出，随着肌纤维数量的增加，肌纤维中每个核的转录回报范围减小，这说明了发育中的肌纤维对核积累建立大小的绝对依赖，以及成人骨骼肌适应性的限制。骨骼肌由合胞体肌纤维组成，每个肌纤维含有数百个细胞核。通过每个肌纤维的细胞核数量的遗传减少，作者证实，更多的细胞核产生更大的细胞，但具有更少细胞核的肌纤维适应性补偿，导致更大的功能性肌纤维结构域。
Mammalian cells exhibit remarkable diversity in cell size, but the factors that regulate establishment and maintenance of these sizes remain poorly understood. This is especially true for skeletal muscle, comprised of syncytial myofibers that each accrue hundreds of nuclei during development. Here, we directly explore the assumed causal relationship between multinucleation and establishment of normal size through titration of myonuclear numbers during mouse neonatal development. Three independent mouse models, where myonuclear numbers were reduced by 75, 55, or 25%, led to the discovery that myonuclei possess a reserve capacity to support larger functional cytoplasmic volumes in developing myofibers. Surprisingly, the results revealed an inverse relationship between nuclei numbers and reserve capacity. We propose that as myonuclear numbers increase, the range of transcriptional return on a per nuclear basis in myofibers diminishes, which accounts for both the absolute reliance developing myofibers have on nuclear accrual to establish size, and the limits of adaptability in adult skeletal muscle. Skeletal muscle is composed of syncytial myofibres, each containing hundreds of nuclei. Through genetic reduction of the number of nuclei per myofibre, the authors confirm that more nuclei produce larger cells but myofibres with fewer nuclei adaptively compensate leading to larger and functional myonuclear domains.
登录
查看更多内容
影响因子：
16.6
作者：
Hansson KA;Eftestøl E;Bruusgaard JC;Juvkam I;Cramer AW;Malthe-Sørenssen A;Millay DP;Gundersen K
通讯作者：
Gundersen K
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
5.5
作者：
Bruusgaard, JC;Liestol, K;Gundersen, K
通讯作者：
Gundersen, K
DOI：
10.1242/dev.167197
发表时间：
2018-10-25
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Bachman JF;Klose A;Liu W;Paris ND;Blanc RS;Schmalz M;Knapp E;Chakkalakal JV
通讯作者：
Chakkalakal JV
影响因子：
5.5
作者：
Jackson, Janna R.;Mula, Jyothi;Dupont-Versteegden, Esther E.
通讯作者：
Dupont-Versteegden, Esther E.