Spatiotemporal and genetic cell lineage tracing of endodermal organogenesis at single-cell resolution [Smart-seq3-RNA-seq-add]

During early mammalian development, the endoderm layer undergoes complex patterning to form the foundations of the respiratory and digestive systems. This intricate process, guided by a series of cell fate decisions, remains only partially understood. Our research introduces a pioneering genetic tracing code across 14 distinct endodermal regions by developing a group of mouse strains. By integrating high-throughput and high-precision single-cell RNA sequencing with sophisticated imaging techniques across various mouse models, we comprehensively resolve the spatiotemporal and genetic lineage differentiation processes of the endoderm at a single-cell resolution. Our findings reveal a previously unrecognized multipotentiality within early endodermal regions for differentiation into diverse organ primordia. Furthermore, this research illuminates the complex and underestimated phenomenon of multiple origins in the development of endodermal organs, prompting a reevaluation of differentiation models for these organs. This work not only advances our understanding of developmental biology, but also has significant implications for regenerative medicine and the development of organoid models, providing new insights into the intricate mechanisms that guide organogenesis. scRNA-seq of tracing lineage for the development of endoderm

在哺乳动物发育早期，内胚层（endoderm）会经历复杂的模式化过程，以构建呼吸系统与消化系统的雏形结构。这一受一系列细胞命运决定调控的精密发育进程，目前仍仅被部分解析。本研究通过构建一组小鼠品系，搭建了覆盖14个独立内胚层区域的首创性遗传追踪谱系体系。研究团队将高通量、高精度的单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）与多种小鼠模型中的尖端成像技术相结合，在单细胞分辨率下全面解析了内胚层的时空动态与遗传谱系分化进程。研究发现，早期内胚层区域中存在此前未被认知的多能性，可分化为多种器官原基。此外，本研究揭示了内胚层器官发育中多起源这一复杂且此前被低估的现象，推动了对这类器官分化模型的重新评估。这项工作不仅加深了我们对发育生物学的理解，还对再生医学与类器官模型开发具有重要意义，为阐明器官发生的精密调控机制提供了全新视角。本数据集为用于内胚层发育谱系追踪的单细胞RNA测序数据