Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
Beijing Advanced Innovation Center for Genomics (ICG), College of Life Sciences, Peking University, Beijing, China.
J Mol Cell Biol. 2019 Jun 1;11(6):435-447. doi: 10.1093/jmcb/mjy064.
Pancreatic endocrine islets are vital for glucose homeostasis. However, the islet developmental trajectory and its regulatory network are not well understood. To define the features of these specification and differentiation processes, we isolated individual islet cells from TgBAC(neurod1:EGFP) transgenic zebrafish and analyzed islet developmental dynamics across four different embryonic stages using a single-cell RNA-seq strategy. We identified proliferative endocrine progenitors, which could be further categorized by different cell cycle phases with the G1/S subpopulation displaying a distinct differentiation potential. We identified endocrine precursors, a heterogeneous intermediate-state population consisting of lineage-primed alpha, beta and delta cells that were characterized by the expression of lineage-specific transcription factors and relatively low expression of terminally differentiation markers. The terminally differentiated alpha, beta, and delta cells displayed stage-dependent differentiation states, which were related to their functional maturation. Our data unveiled distinct states, events and molecular features during the islet developmental transition, and provided resources to comprehensively understand the lineage hierarchy of islet development at the single-cell level.
胰岛内分泌细胞对于葡萄糖稳态至关重要。然而，胰岛的发育轨迹及其调控网络还不是很清楚。为了定义这些特化和分化过程的特征，我们从 TgBAC(neurod1:EGFP)转基因斑马鱼中分离了单个胰岛细胞，并使用单细胞 RNA-seq 策略分析了四个不同胚胎阶段的胰岛发育动态。我们鉴定出增殖性内分泌祖细胞，它们可以根据不同的细胞周期阶段进一步分类，其中 G1/S 亚群显示出明显的分化潜能。我们鉴定出内分泌前体细胞，这是一个异质的中间状态群体，由谱系启动的 alpha、beta 和 delta 细胞组成，其特征是表达谱系特异性转录因子和相对较低的终末分化标记物。终末分化的 alpha、beta 和 delta 细胞显示出与功能成熟相关的阶段依赖性分化状态。我们的数据揭示了胰岛发育过渡过程中的不同状态、事件和分子特征，并提供了资源来全面了解胰岛发育在单细胞水平上的谱系层次结构。
