间充质干细胞
支气管肺发育不良
生物
肺
高氧
人口
转录组
免疫学
间质细胞
骨髓
癌症研究
病理
细胞生物学
基因表达
医学
基因
遗传学
胎龄
内科学
怀孕
环境卫生
作者
Ivana Mižíková,Flore Lesage,Chanèle Cyr-Depauw,David P. Cook,Maria Hurskainen,Satu Hänninen,Arul Vadivel,Pauline Bardin,Sen Zhong,Olli Carpén,Barbara C. Vanderhyden,Bernard Thébaud
出处
期刊:Stem Cells
[Wiley]
日期:2022-01-24
卷期号:40 (5): 479-492
被引量:7
标识
DOI:10.1093/stmcls/sxab023
摘要
Late lung development is a period of alveolar and microvascular formation, which is pivotal in ensuring sufficient and effective gas exchange. Defects in late lung development manifest in premature infants as a chronic lung disease named bronchopulmonary dysplasia (BPD). Numerous studies demonstrated the therapeutic properties of exogenous bone marrow and umbilical cord-derived mesenchymal stromal cells (MSCs) in experimental BPD. However, very little is known regarding the regenerative capacity of resident lung MSCs (L-MSCs) during normal development and in BPD. In this study we aimed to characterize the L-MSC population in homeostasis and upon injury. We used single-cell RNA sequencing (scRNA-seq) to profile in situ Ly6a+ L-MSCs in the lungs of normal and O2-exposed neonatal mice (a well-established model to mimic BPD) at 3 developmental timepoints (postnatal days 3, 7, and 14). Hyperoxia exposure increased the number and altered the expression profile of L-MSCs, particularly by increasing the expression of multiple pro-inflammatory, pro-fibrotic, and anti-angiogenic genes. In order to identify potential changes induced in the L-MSCs transcriptome by storage and culture, we profiled 15 000 Ly6a+ L-MSCs after in vitro culture. We observed great differences in expression profiles of in situ and cultured L-MSCs, particularly those derived from healthy lungs. Additionally, we have identified the location of Ly6a+/Col14a1+ L-MSCs in the developing lung and propose Serpinf1 as a novel, culture-stable marker of L-MSCs. Finally, cell communication analysis suggests inflammatory signals from immune and endothelial cells as main drivers of hyperoxia-induced changes in L-MSCs transcriptome.
科研通智能强力驱动
Strongly Powered by AbleSci AI