National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2023 Sep 2;14(1):5354. doi: 10.1038/s41467-023-40893-8.
Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity.
了解胰腺的发育过程可以为更好地治疗胰腺疾病提供线索。然而，早期人类胰腺的分子异质性和发育轨迹仍未得到充分探索。在这里，我们对从早期胚胎中获得的人类胚胎胰腺组织进行了大规模的单细胞 RNA 测序和单细胞转座酶可及染色质测序分析。我们揭示了主要细胞类型的分子异质性、发育轨迹和调控网络。结果表明，人类背侧胰腺多能细胞表现出与腹侧多能细胞不同的基因表达模式。鉴定出了在人类中产生腹侧多能细胞的胰胆管祖细胞。来自间质细胞的 Notch 和 MAPK 信号调节多能细胞向干和导管细胞的分化。值得注意的是，我们鉴定了具有不同分化潜力的内分泌祖细胞亚群。尽管人类和小鼠的发育轨迹在很大程度上是保守的，但也确定了一些不同的基因表达模式。总的来说，我们提供了早期人类胰腺发育的全面图谱，以了解其谱系转变和分子复杂性。
