Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
Development. 2020 Jan 17;147(2):dev181032. doi: 10.1242/dev.181032.
Alveologenesis is an essential developmental process that increases the surface area of the lung through the formation of septal ridges. In the mouse, septation occurs postnatally and is thought to require the alveolar myofibroblast (AMF). Though abundant during alveologenesis, markers for AMFs are minimally detected in the adult. After septation, the alveolar walls thin to allow efficient gas exchange. Both loss of AMFs or retention and differentiation into another cell type during septal thinning have been proposed. Using a novel allele to lineage trace AMFs, we demonstrate that most AMFs are developmentally cleared during alveologenesis. Lung mesenchyme also contains other poorly described cell types, including alveolar lipofibroblasts (ALF). We show that marks both AMFs as well as ALFs, and lineage tracing shows that ALFs are retained in adult alveoli while AMFs are lost. We further show that multiple immune cell populations contain lineage-labeled particles, suggesting a phagocytic role in the clearance of AMFs. The demonstration that the AMF lineage is depleted during septal thinning through a phagocytic process provides a mechanism for the clearance of a transient developmental cell population.
肺泡发生是一个重要的发育过程，通过形成隔膜嵴增加肺的表面积。在小鼠中，分隔发生在出生后，被认为需要肺泡肌成纤维细胞（AMF）。尽管在肺泡发生过程中 AMF 丰富，但在成人中很少检测到 AMF 的标志物。分隔后，肺泡壁变薄以实现有效的气体交换。在隔层变薄过程中，有人提出 AMF 的丢失或保留以及分化为另一种细胞类型。使用一种新型的 等位基因来追踪 AMF，我们证明在肺泡发生过程中，大多数 AMF 是在发育过程中被清除的。肺间质还包含其他描述较少的细胞类型，包括肺泡脂肪成纤维细胞（ALF）。我们表明 标记 AMF 和 ALF，谱系追踪表明 ALF 在成年肺泡中保留，而 AMF 丢失。我们进一步表明，多个免疫细胞群体含有谱系标记的颗粒，这表明 AMF 的清除可能涉及吞噬作用。通过吞噬作用来清除 AMF 的短暂发育细胞群体，这一过程为 AMF 谱系在隔层变薄过程中被清除提供了一种机制。
