Institut de Systématique, Evolution, Biodiversité (ISYEB), UMR 7205, Sorbonne Université, Muséum National d'histoire Naturelle, CNRS, EPHE, 7 Quai St-Bernard, F-75252, Paris Cedex 05, France.
Center for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
BMC Mol Cell Biol. 2021 Oct 6;22(1):51. doi: 10.1186/s12860-021-00388-0.
Apoptosis is a caspase regulated cell death present in all metazoans defined by a conserved set of morphological features. A well-described function of apoptosis is the removal of excessive cells during development and homeostasis. Recent studies have shown an unexpected signalling property of apoptotic cells, affecting cell fate and/or behaviour of neighbouring cells. In contrast to the apoptotic function of cell elimination, this new role of apoptosis is not well understood but seems caspase-dependent. To deepen our understanding of apoptotic functions, it is necessary to work on a biological model with a predictable apoptosis pattern affecting cell fate and/or behaviour. The tunicate Ciona intestinalis has a bi-phasic life cycle with swimming larvae which undergo metamorphosis after settlement. Previously, we have shown that the tail regression step during metamorphosis, characterized by a predictable polarized apoptotic wave, ensures elimination of most tail cells and controls primordial germ cells survival and migration.
We performed differential transcriptomic analysis between control metamorphosing larvae and larvae treated with the pan-caspase inhibitor Z-VAD-fmk in order to explore the transcriptional control of apoptotic cells on neighbouring cells that survive and migrate. When caspase activity was impaired, genes known to be involved in metamorphosis were downregulated along with other implicated in cell migration and survival molecular pathways.
We propose these results as a confirmation that apoptotic cells can control surrounding cells fate and as a reference database to explore novel apoptotic functions in animals, including those related to migration and differentiation.
凋亡是一种在所有后生动物中都存在的 caspase 调控的细胞死亡方式,其特征是具有一套保守的形态学特征。凋亡的一个众所周知的功能是在发育和稳态过程中清除过多的细胞。最近的研究表明,凋亡细胞具有一种出乎意料的信号传递特性,影响邻近细胞的命运和/或行为。与细胞消除的凋亡功能相反,凋亡的这种新作用尚不清楚,但似乎依赖于 caspase。为了更深入地了解凋亡的功能,有必要在一个具有可预测的凋亡模式影响细胞命运和/或行为的生物学模型上进行研究。海鞘 Ciona intestinalis 具有双相生命周期,有游动的幼虫,在定殖后经历变态。以前,我们已经表明,变态过程中的尾部退化阶段,其特征是可预测的极化凋亡波,确保了大多数尾部细胞的消除,并控制原始生殖细胞的存活和迁移。
我们对对照变态幼虫和用泛 caspase 抑制剂 Z-VAD-fmk 处理的幼虫进行了差异转录组分析,以探索凋亡细胞对存活和迁移的邻近细胞的转录控制。当 caspase 活性受到抑制时,已知参与变态的基因以及其他参与细胞迁移和存活的分子途径的基因下调。
我们提出这些结果作为对凋亡细胞可以控制周围细胞命运的证实,并作为一个参考数据库,以探索动物中凋亡的新功能,包括那些与迁移和分化相关的功能。