Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Graduate School of Biomedical Sciences , The University of Texas MD Anderson Cancer Center UTHealth, Houston, Texas 77030, USA.
Development. 2022 Mar 15;149(6). doi: 10.1242/dev.200081. Epub 2022 Mar 18.
The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined morphologically and molecularly. Leveraging single-cell RNA-sequencing, 3D imaging and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium and interstitium, respectively. From proximal to distal: the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts - ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP and LGR6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; and the interstitial axis, residing between the epithelial and vascular trees and sharing the marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium, which are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals a distinct morphology of mesenchymal cell populations. This classification provides a conceptual and experimental framework applicable to other organs.
中胚层由异质性细胞群体组成，这些细胞群体支持邻近的结构，是细胞间信号传递的重要组成部分，但在形态和分子水平上定义不明确。利用单细胞 RNA 测序、3D 成像和谱系追踪，我们将小鼠肺中胚层分为三个近-远轴，分别与内皮细胞、上皮细胞和间质相关。从近端到远端：血管轴包括血管平滑肌细胞和周细胞，它们随着小动脉和小静脉分支为毛细血管而转变；上皮轴包括气道平滑肌细胞和两种肌成纤维细胞群体 - 导管肌成纤维细胞，围绕肺泡导管，以 CDH4、HHIP 和 LGR6 为标记，在肺泡发生后仍然存在，和肺泡肌成纤维细胞，围绕肺泡，以 PDGFRA 的高表达为标记，经历发育性细胞凋亡；间质轴位于上皮和血管树之间，共享 MEOX2 标记物，包括支气管血管束和肺泡间质中的成纤维细胞，它们分别以 IL33/DNER/PI16 和 Wnt2 为标记。单细胞成像揭示了间充质细胞群体的独特形态。这种分类为其他器官提供了一个概念和实验框架。
