中国科学院广州生物医药卫生研究院彭广敦研究组报道了发育中小鼠肺的时空转录组图谱。相关论文于2025年3月10日发表在《科学通报》杂志上。

在这里，该团队应用高通量空间转录组学来全面评估由两个关键发育事件组成的无主题肺发育：分支形态发生和肺泡发生。在整合已发表的单细胞RNA测序数据的基础上，该研究组首先生成了从E12.5到P0的无主题肺发育空间分子图谱，并确定了10个对肺功能组织至关重要的空间结构域。

此外，研究团队创建了连接E12.5-P0肺中相邻时间点空间细胞的谱系轨迹，并探索了每个谱系规范的TF（转录因子）调控网络。研究小组观察到肺气道在发育中的建立，伴随着近端-远端模式，具有明显的基因表达特征，信号景观和转录因子富集。研究小组描述了出生前后发育后期成熟状态差异的肺泡生态位异质性，并证明了Angpt2和Epha3等基因的差异表达，这些基因可能在肺泡形成过程中发挥关键作用。此外，多种信号通路，包括ANGPT、VEGF和EPHA，在更成熟的肺泡生态位中表现出更高的水平。总的来说，通过将空间转录组与相应的单细胞转录组数据相结合，该研究组提供了一个完整的motheme肺发育分子图谱，并进行了详细的分子结构域注释和交流，这将为理解人类肺发育和呼吸再生医学铺平道路。

研究人员表示，哺乳动物肺的功能发育是一个复杂的过程，依赖于多种细胞类型及其状态的时空组织。然而，一个全面的发育中的肺的时空转录组图谱尚未被报道。

附：英文原文

Title: Spatiotemporal transcriptome atlas of developing mouse lung

Author: Guizhong Cui c e, Shengbao Suo d e, Guangdun Peng b

Issue&Volume: 2025/03/10

Abstract: The functional development of the mammalian lung is a complex process that relies on the spatial and temporal organization of multiple cell types and their states. However, a comprehensive spatiotemporal transcriptome atlas of the developing lung has not yet been reported. Here we apply high-throughput spatial transcriptomics to allow for a comprehensive assessment of mouse lung development comprised of two critical developmental events: branching morphogenesis and alveologenesis. We firstly generate a spatial molecular atlas of mouse lung development spanning from E12.5 to P0 based on the integration of published single cell RNA-sequencing data and identify 10 spatial domains critical for functional lung organization. Furthermore, we create a lineages trajectory connecting spatial clusters from adjacent time points in E12.5–P0 lungs and explore TF (transcription factor) regulatory networks for each lineage specification. We observe the establishment of pulmonary airways within the developing lung, accompanied by the proximal–distal patterning with distinct characteristics of gene expression, signaling landscape and transcription factors enrichment. We characterize the alveolar niche heterogeneity with maturation state differences during the later developmental stage around birth and demonstrate differentially expressed genes, such as Angpt2 and Epha3, which may perform a critical role during alveologenesis. In addition, multiple signaling pathways, including ANGPT, VEGF and EPHA, exhibit increased levels in more maturing alveolar niche. Collectively, by integrating the spatial transcriptome with corresponding single-cell transcriptome data, we provide a comprehensive molecular atlas of mouse lung development with detailed molecular domain annotation and communication, which would pave the way for understanding human lung development and respiratory regeneration medicine.

DOI: 10.1016/j.scib.2025.03.012

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927325002403