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脊索动物胚胎发生的分子谱系的单细胞分析。

A single-cell analysis of the molecular lineage of chordate embryogenesis.

机构信息

Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200123, China.

Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.

出版信息

Sci Adv. 2020 Nov 4;6(45). doi: 10.1126/sciadv.abc4773. Print 2020 Nov.

Abstract

Progressive unfolding of gene expression cascades underlies diverse embryonic lineage development. Here, we report a single-cell RNA sequencing analysis of the complete and invariant embryonic cell lineage of the tunicate from fertilization to the onset of gastrulation. We reconstructed a developmental landscape of 47 cell types over eight cell cycles in the wild-type embryo and identified eight fate transformations upon fibroblast growth factor (FGF) inhibition. For most FGF-dependent asymmetric cell divisions, the bipotent mother cell displays the gene signature of the default daughter fate. In convergent differentiation of the two notochord lineages, we identified additional gene pathways parallel to the master regulator / Last, we showed that the defined cell types can be matched to E6.5-E8.5 stage mouse cell types and display conserved expression of limited number of transcription factors. This study provides a high-resolution single-cell dataset to understand chordate early embryogenesis and cell lineage differentiation.

摘要

基因表达级联的渐进式展开是胚胎谱系多样化发育的基础。在这里,我们报告了对从受精到原肠胚形成开始的 被囊动物完整且不变的胚胎细胞谱系进行的单细胞 RNA 测序分析。我们在野生型胚胎中重建了 8 个细胞周期中 47 种细胞类型的发育景观,并在成纤维细胞生长因子(FGF)抑制后鉴定出 8 种命运转变。对于大多数 FGF 依赖性不对称细胞分裂,双潜能母细胞显示出默认子细胞命运的基因特征。在两个脊索谱系的趋同分化中,我们鉴定了与主调控因子 / 平行的其他基因途径。最后,我们表明,定义的 细胞类型可以与 E6.5-E8.5 阶段的小鼠细胞类型匹配,并显示有限数量转录因子的保守表达。这项研究提供了一个高分辨率的单细胞数据集,用于理解脊索动物早期胚胎发生和细胞谱系分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d8c/7673699/7233518571a6/abc4773-F1.jpg

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