Domínguez-Bautista Jorge Antolio, Acevo-Rodríguez Pilar Sarah, Castro-Obregón Susana
División de Neurociencias, Instituto de Fisiología Celular, UNAM, Mexico City, Mexico.
Front Cell Dev Biol. 2021 Jan 26;9:587096. doi: 10.3389/fcell.2021.587096. eCollection 2021.
Programmed cell senescence is a cellular process that seems to contribute to embryo development, in addition to cell proliferation, migration, differentiation and programmed cell death, and has been observed in evolutionary distant organisms such as mammals, amphibians, birds and fish. Programmed cell senescence is a phenotype similar to stress-induced cellular senescence, characterized by the expression of the cell cycle inhibitors p21 and p16, increased activity of a lysosomal enzyme with beta-galactosidase activity (coined senescence-associated beta-galactosidase) and secretion of growth factors, interleukins, chemokines, metalloproteases, etc., collectively known as a senescent-associated secretory phenotype that instructs surrounding tissue. How wide is the distribution of programmed cell senescence during mouse development and its specific mechanisms to shape the embryo are still poorly understood. Here, we investigated whether markers of programmed cell senescence are found in the developing mouse spinal cord and notochord. We found discrete areas and developmental windows with high senescence-associated beta galactosidase in both spinal cord and notochord, which was reduced in mice embryos developed in the presence of the senolytic ABT-263. Expression of p21 was documented in epithelial cells of the spinal cord and the notochord, while p16 was observed in motoneurons. Treatment with the senolytic ABT-263 decreased the number of motoneurons, supporting their senescent phenotype. Our data suggest that a subpopulation of motoneurons in the developing spinal cord, as well as some notochord cells undergo programmed cell senescence.
程序性细胞衰老似乎是一种细胞过程，除了细胞增殖、迁移、分化和程序性细胞死亡外，它还对胚胎发育有贡献，并且在进化上距离较远的生物，如哺乳动物、两栖动物、鸟类和鱼类中都有观察到。程序性细胞衰老与应激诱导的细胞衰老类似，其特征是细胞周期抑制剂p21和p16的表达、具有β-半乳糖苷酶活性的溶酶体酶（即衰老相关β-半乳糖苷酶）活性增加以及生长因子、白细胞介素、趋化因子、金属蛋白酶等的分泌，这些统称为衰老相关分泌表型，可对周围组织产生影响。在小鼠发育过程中，程序性细胞衰老的分布范围有多广以及其塑造胚胎的具体机制仍知之甚少。在这里，我们研究了在发育中的小鼠脊髓和脊索中是否能找到程序性细胞衰老的标志物。我们在脊髓和脊索中都发现了与衰老相关β-半乳糖苷酶含量高的离散区域和发育窗口，在存在衰老细胞裂解剂ABT-263的情况下发育的小鼠胚胎中，这种情况有所减少。脊髓和脊索的上皮细胞中记录到了p21的表达，而在运动神经元中观察到了p16的表达。用衰老细胞裂解剂ABT-263处理会减少运动神经元的数量，这支持了它们的衰老表型。我们的数据表明，发育中的脊髓中的一部分运动神经元以及一些脊索细胞会经历程序性细胞衰老。
