Université de Paris, Institut Cochin, INSERM, CNRS, 24 rue du Fg St Jacques, F-75014 Paris, France.
Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime, 791-0295, Japan.
Development. 2020 Oct 9;147(19):dev185975. doi: 10.1242/dev.185975.
expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the sine oculis-related homeobox - genes in vertebrates. , , and are expressed in the muscle lineage. Here, we tested the hypothesis that and could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in and knockout mice (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior muscle. Mutant stem cells contribute to hypotrophic myofibers that are not innervated but retain the ability to self-renew.
表达标记在胚胎发生过程中控制进入肌生成程序和出现 PAX7+细胞的遗传决定因素知之甚少。SIX 同源盒蛋白由脊椎动物的 sine oculis 相关同源盒基因编码。、、和在肌肉谱系中表达。在这里，我们检验了假说，即 和 可以参与肌源性干细胞的发生。我们发现，在 E18 时， 缺失和 缺失的小鼠（s1s4KO）中，较少的 PAX7+细胞占据肌纤维与其相关基底膜之间的卫星细胞位置。然而，在双突变胚胎的背侧区域仍然存在剩余的肌肉块中检测到 PAX7+细胞，并且能够分裂并有助于肌肉生长。为了进一步表征 s1s4KO PAX7+细胞的特性，我们分析了它们的转录组，并在成年再生胫骨前肌中移植后测试了它们的特性。突变的干细胞有助于形成未受神经支配但仍能自我更新的萎缩肌纤维。
