Department of Pediatrics, University of California, San Diego, La Jolla, United States.
Laboratory of Genetics, Department of Medical Genetics, University of Wisconsin-Madison, Madison, United States.
Elife. 2018 Sep 4;7:e36865. doi: 10.7554/eLife.36865.
-expressing () cells have been implicated as progenitors in many mesenchymal tissues. To determine lineage potential, we generated knockin mice using CRISPR/Cas9. During lung maturation, counter to a prior study reporting that + cells give rise equally to myofibroblasts and lipofibroblasts, lineage tracing using mice indicated that ~95% of the lineaged cells are myofibroblasts. Genetic ablation of cells using -driven diphtheria toxin (DTA) led to alveolar simplification, demonstrating that these cells are essential for building the gas exchange surface area. In the adult bleomycin model of lung fibrosis, lineaged cells increased to contribute to pathological myofibroblasts. In contrast, in a neonatal hyperoxia model of bronchopulmonary dysplasia (BPD), lineaged cells decreased and do not substantially contribute to pathological myofibroblasts. Our findings revealed complexity in the behavior of the -lineaged cells as exemplified by their distinct contributions to myofibroblasts in normal maturation, BPD and adult fibrosis.
表达（）细胞已被认为是许多间充质组织的祖细胞。为了确定谱系潜能，我们使用 CRISPR/Cas9 生成了 敲入小鼠。在肺成熟过程中，与先前报道的+细胞同等地产生肌成纤维细胞和脂肪成纤维细胞的研究相反，使用 小鼠进行的谱系追踪表明，约 95%的谱系细胞是肌成纤维细胞。使用 -驱动的白喉毒素（DTA）对 细胞进行遗传消融导致肺泡简化，表明这些细胞对于构建气体交换表面积是必不可少的。在博来霉素诱导的肺纤维化的成年模型中，谱系细胞增加以促进病理性肌成纤维细胞的形成。相比之下，在新生儿高氧诱导的支气管肺发育不良（BPD）模型中，谱系细胞减少，并且不会大量促进病理性肌成纤维细胞的形成。我们的研究结果揭示了 -谱系细胞行为的复杂性，例如它们在正常成熟、BPD 和成人纤维化中对肌成纤维细胞的不同贡献。
