State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
Guangzhou National Laboratory, Guangzhou, 510005, Guangdong Province, China.
Nat Commun. 2023 Sep 14;14(1):5675. doi: 10.1038/s41467-023-41482-5.
Understanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic molecular trajectories of cell lineages across a series of developmental stages of gastrulation. Through computational modeling, we constructed at single-cell resolution, a spatio-temporal transcriptome of cell populations in the germ-layers of gastrula-stage mouse embryos. This molecular atlas enables the inference of molecular network activity underpinning the specification and differentiation of the germ-layer tissue lineages. Heterogeneity analysis of cellular composition at defined positions in the epiblast revealed progressive diversification of cell types. The single-cell transcriptome revealed an enhanced BMP signaling activity in the right-side mesoderm of late-gastrulation embryo. Perturbation of asymmetric BMP signaling activity at late gastrulation led to randomization of left-right molecular asymmetry in the lateral mesoderm of early-somite-stage embryo. These findings indicate the asymmetric BMP activity during gastrulation may be critical for the symmetry breaking process.
理解原肠胚形成过程中初级胚层发育过程中谱系多样化和组织模式形成的分子驱动因素，需要深入了解细胞谱系在原肠胚形成的一系列发育阶段中动态分子轨迹。通过计算建模，我们以单细胞分辨率构建了原肠胚期小鼠胚胎胚层细胞群体的时空转录组。这个分子图谱使得可以推断出支持胚层组织谱系特化和分化的分子网络活性。在胚外中胚层的定义位置对细胞组成进行异质性分析，揭示了细胞类型的逐渐多样化。单细胞转录组揭示了晚期原肠胚胚胎右侧中胚层中 BMP 信号活性增强。晚期原肠胚时不对称 BMP 信号活性的扰动导致早期体节胚胎侧中胚层中左右分子不对称性的随机化。这些发现表明原肠胚形成过程中不对称的 BMP 活性对于对称破缺过程可能是关键的。
