Aix-Marseille Université, CNRS UMR 7288, IBDM, Turing Centre for Living Systems, Marseille, France.
Aix-Marseille Université, LIS, UMR 7020, Turing Centre for Living Systems, Marseille, France.
Nat Commun. 2024 Nov 4;15(1):9512. doi: 10.1038/s41467-024-53612-8.
The vertebrate heart tube extends by progressive addition of epithelial second heart field (SHF) progenitor cells from the dorsal pericardial wall. The interplay between epithelial mechanics and genetic mechanisms during SHF deployment is unknown. Here, we present a quantitative single-cell morphometric analysis of SHF cells during heart tube extension, including force inference analysis of epithelial stress. Joint spatial Principal Component Analysis reveals that cell orientation and stress direction are the main parameters defining apical cell morphology and distinguishes cells adjacent to the arterial and venous poles. Cell shape and mechanical forces display a dynamic relationship during heart tube formation. Moreover, while the T-box transcription factor Tbx1 is necessary for cell orientation towards the arterial pole, activation of Tbx5 in the posterior SHF correlates with the establishment of epithelial stress and SHF deletion of Tbx5 relaxes the progenitor epithelium. Integrating findings from cell-scale feature patterning and mechanical stress provides new insights into cardiac morphogenesis.
脊椎动物心脏管通过从背侧心包壁渐进性添加上皮第二心脏场 (SHF) 祖细胞来延伸。在 SHF 部署过程中,上皮力学和遗传机制之间的相互作用尚不清楚。在这里,我们对心脏管延伸过程中的 SHF 细胞进行了定量的单细胞形态计量分析,包括上皮应激的力推断分析。联合空间主成分分析表明,细胞方向和应力方向是定义顶端细胞形态的主要参数,并区分了靠近动脉和静脉极的细胞。在心脏管形成过程中,细胞形状和机械力呈现动态关系。此外,虽然 T 盒转录因子 Tbx1 对于细胞朝向动脉极的方向是必需的,但是后部 SHF 中的 Tbx5 的激活与上皮应激的建立相关,并且 SHF 中 Tbx5 的缺失会使祖细胞上皮松弛。将细胞尺度特征模式和机械应激的发现整合在一起,为心脏形态发生提供了新的见解。
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