Cell-intrinsic differences between human airway epithelial cells from children and adults.

Cell-intrinsic differences between human airway epithelial cells from children and adults.
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DOI:
10.1016/j.isci.2022.105409
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发表时间:
2022-11-18
期刊:
影响因子:
5.8
通讯作者:
Janes, Sam M.
Janes, Sam M.
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Maughan, Elizabeth F.;Hynds, Robert E.;Pennycuick, Adam;Nigro, Ersilia;Gowers, Kate H. C.;Denais, Celine;Gomez-Lopez, Sandra;Lazarus, Kyren A.;Orr, Jessica C.;Pearce, David R.;Clarke, Sarah E.;Lee, Dani Do Hyang;Woodall, Maximillian N. J.;Masonou, Tereza;Case, Katie-Marie;Teixeira, Vitor H.;Hartley, Benjamin E.;Hewitt, Richard J.;Al Yaghchi, Chadwan;Sandhu, Gurpreet S.;Birchall, Martin A.;O'Callaghan, Christopher;Smith, Claire M.;De Coppi, Paolo;Butler, Colin R.;Janes, Sam M.

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气道上皮是一种保护性屏障,由基底干细胞的自我更新和分化维持。年龄增长是慢性肺部疾病的主要危险因素,但很少有研究探讨气道上皮细胞中与年龄相关的分子或功能变化。我们从儿科和成人供体的组织学正常的气管支气管部位检索上皮活检,并比较其细胞组成和基因表达谱(在激光捕获显微切割的整个上皮,荧光激活细胞分选的基底细胞和细胞培养中的基底细胞)。组织学上,小儿和成人气管支气管上皮的组成相似。我们在RNA测序研究中观察到年龄相关的变化,包括儿科上皮细胞中干扰素相关基因表达的增加。在细胞培养中,儿科细胞具有更高的集落形成能力,在体外持续生长,并在直接竞争性增殖试验中胜过成人细胞。我们的研究结果表明,儿童和成人的气道上皮细胞在稳态和增殖状态之间存在细胞内在差异。儿童和成人的人气道上皮细胞组成相似儿童气道粘膜中干扰素相关转录谱原代细胞培养中儿童细胞比成人细胞更容易扩增医学科学;儿科学;分子生物学
The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture). Histologically, pediatric and adult tracheobronchial epithelium was similar in composition. We observed age-associated changes in RNA sequencing studies, including higher interferon-associated gene expression in pediatric epithelium. In cell culture, pediatric cells had higher colony formation ability, sustained in vitro growth, and outcompeted adult cells in a direct competitive proliferation assay. Our results demonstrate cell-intrinsic differences between airway epithelial cells from children and adults in both homeostatic and proliferative states. Human airway epithelium was similar in composition in children and adults Interferon-associated transcriptional profile in pediatric airway mucosa Pediatric cells expanded more readily than adult cells in primary cell culture Medical science; Pediatrics; Molecular biology
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