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

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 Please note that total 25,847 samples (represented in 140 condensed sample records) were included in the current study. The individual sample and raw file information is included in the sample_information.txt, SRR_filenames.txt.在哺乳动物早期发育阶段，内胚层（endoderm）会经历复杂的模式形成过程，进而构建呼吸系统与消化系统的发育基础。这一受一系列细胞命运决定事件调控的复杂过程，目前仍仅被部分阐明。本研究通过构建一系列小鼠品系（mouse strains），建立了覆盖14个独立内胚层区域的首创性遗传谱系追踪标记体系。本研究将高通量、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先进成像技术相结合，以单细胞分辨率全面解析了内胚层的时空动态特征与遗传谱系分化过程。研究结果揭示了早期内胚层区域中此前未被认知的多向分化潜能——其可分化为多种器官原基（organ primordia）。此外，本研究阐明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。本研究不仅加深了我们对发育生物学的认知，还为再生医学与类器官模型（organoid models）的开发提供了重要参考，并为解析调控器官发生（organogenesis）的复杂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。请注意，本研究共纳入25847个样本（对应140条精简样本记录）。单个样本与原始文件的相关信息已收录于sample_information.txt与SRR_filenames.txt文件中。