A spatiotemporal cell atlas of cardiopulmonary progenitor cell allocation during development

The heart and lung co-orchestrate their development during organogenesis. The mesoderm surrounding both the developing heart and anterior foregut endoderm provides instructive cues guiding cardiopulmonary development. Additionally, it serves as a source of cardiopulmonary progenitor cells (CPPs) expressing Wnt2 that give rise to both cardiac and lung mesodermal cell lineages. Despite its critical importance to both heart and lung development, mechanisms guiding CPP specification are unclear. To address this, we lineage traced Wnt2+ CPPs at E8.5 and performed single cell RNA sequencing (scRNA-seq) on collected progeny across the developmental lifespan. Using computational analyses, we created a CPP-derived cell atlas that revealed a previously underappreciated spectrum of CPP-derived cell lineages, including all lung mesodermal lineages, ventricular cardiomyocytes (CMs), and epicardial and pericardial cells. Integrating spatial mapping with computational cell trajectory analysis and transcriptional profiling, we have provided a potential molecular and cellular roadmap for cardiopulmonary development. 

This record contains a gzipped anndata h5ad (hdf5) file corresponding to the scRNA-seq data generated during this study. Raw gene expression counts, as well as normalized counts, are provided as values in the `layers` attribute of the anndata object. Cell annotations and projection coordinates are similarly provided in the `obs` and `obsm` attributes of the object, respectively. The AnnData and Scanpy python libraries are required to load and re-process these data.

在器官发生过程中，心脏与肺脏协同发育。发育中的心脏及前肠内胚层周围的中胚层可提供指导性信号，调控心肺系统的发育。此外，该中胚层还是表达Wnt2的心肺祖细胞（cardiopulmonary progenitor cells, CPPs）的来源，这类祖细胞可分化为心脏和肺脏的中胚层细胞谱系。尽管其对心脏与肺脏发育均至关重要，但调控CPP特化的分子机制仍不明晰。

为解决这一科学问题，我们在胚胎发育第8.5天（E8.5）对Wnt2+ CPPs进行了谱系追踪，并对整个发育周期中收集的子代细胞开展了单细胞RNA测序（single cell RNA sequencing, scRNA-seq）。通过计算分析，我们构建了CPP来源的细胞图谱，该图谱揭示了此前未被充分认知的CPP衍生细胞谱系谱，涵盖所有肺脏中胚层谱系、心室心肌细胞（cardiomyocytes, CMs）以及心外膜和心包膜细胞。我们将空间定位与计算细胞轨迹分析、转录组谱分析相结合，为心肺发育提供了潜在的分子与细胞路线图。

本数据集包含一份经gzip压缩的anndata格式h5ad（HDF5）文件，对应本研究中生成的scRNA-seq数据。AnnData对象的`layers`属性中存储了原始基因表达计数与标准化计数数据；细胞注释与投影坐标分别存储于该对象的`obs`与`obsm`属性中。加载并重新处理这些数据需依赖AnnData与Scanpy这两个Python库。