瑞典斯德哥尔摩大学Christos Samakovlis和Mats Nilsson课题组定义了人类胚胎肺细胞异质性的发育起源。2023年1月16日出版的《自然—细胞生物学》发表了这项成果。

为了阐明细胞异质性的起源和机制，他们创建了早期人类肺发育的综合图集。他们报告了83个细胞状态和几个空间解析的发育轨迹，并预测了定义的组织壁龛内的细胞相互作用。他们将单细胞RNA测序和空间解析转录组学集成到一个基于网络的交互式探索开放平台中。他们显示了不同的基因表达程序，伴随着近端上皮分泌和神经内分泌细胞类型的细胞分化和成熟的连续事件。

他们定义了支气管维管束中与气道平滑肌相关的气道成纤维细胞的起源，并描述了Schwann细胞祖细胞到内在副交感神经控制支气管收缩的轨迹。他们的图谱为进一步研究提供了丰富的资源，并为定义导致肺部疾病的稳态和修复机制的偏差提供了参考。

据介绍，肺包含许多特化细胞类型，在组织功能和完整性中具有不同的作用。

附：英文原文

Title: A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung

Author: Sountoulidis, Alexandros, Marco Salas, Sergio, Braun, Emelie, Avenel, Christophe, Bergenstrhle, Joseph, Theelke, Jonas, Vicari, Marco, Czarnewski, Paulo, Liontos, Andreas, Abalo, Xesus, Andrusivov, aneta, Mirzazadeh, Reza, Asp, Michaela, Li, Xiaofei, Hu, Lijuan, Sariyar, Sanem, Martinez Casals, Anna, Ayoglu, Burcu, Firsova, Alexandra, Michalsson, Jakob, Lundberg, Emma, Whlby, Carolina, Sundstrm, Erik, Linnarsson, Sten, Lundeberg, Joakim, Nilsson, Mats, Samakovlis, Christos

Issue&Volume: 2023-01-16

Abstract: The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a comprehensive topographic atlas of early human lung development. Here we report 83 cell states and several spatially resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated single-cell RNA sequencing and spatially resolved transcriptomics into a web-based, open platform for interactive exploration. We show distinct gene expression programmes, accompanying sequential events of cell differentiation and maturation of the secretory and neuroendocrine cell types in proximal epithelium. We define the origin of airway fibroblasts associated with airway smooth muscle in bronchovascular bundles and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

DOI: 10.1038/s41556-022-01064-x

Source: https://www.nature.com/articles/s41556-022-01064-x