Smoking shifts human small airway epithelium club cells toward a lesser differentiated population.
Smoking shifts human small airway epithelium club cells toward a lesser differentiated population.
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DOI：
10.1038/s41525-021-00237-1
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发表时间：
2021-09-08
影响因子：
5.3
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Rostami MR;LeBlanc MG;Strulovici-Barel Y;Zuo W;Mezey JG;O'Beirne SL;Kaner RJ;Leopold PL;Crystal RG
俱乐部细胞，一种小气道上皮（SAE）细胞，在人类肺宿主防御中起核心作用。我们假设可能存在具有不同功能的俱乐部细胞亚群。通过单细胞RNA测序评估健康非吸烟者和健康吸烟者的SAE，无监督聚类显示SCGCB 1A 1 + KRT 5loMUC 5AC − club细胞亚群。SAE组织切片、刷拭SAE细胞和体外气液界面培养物的评价支持俱乐部细胞异质性。三个亚群包括：（1）祖细胞;（2）增殖细胞;和（3）效应俱乐部细胞。相对于其他俱乐部细胞群体，祖俱乐部细胞群体表达高水平的线粒体、核糖体蛋白和KRT 5，并且包括导致粘液细胞产生的分化分支点。小的增殖群体表达高水平的细胞周期蛋白和增殖标记物。效应俱乐部细胞簇表达与宿主防御、异生物质代谢和与俱乐部细胞功能相关的屏障功能相关的基因。吸烟者与非吸烟者的比较表明，吸烟限制了所有三个亚群的分化程度，并改变了效应细胞群中含有SAM指向结构域的Ets转录因子（SPDEF）调节的转录，导致粘液细胞产生的分支点位置发生变化，这是吸烟者中效应俱乐部细胞减少和粘液细胞增加的一个可能解释。这些观察结果提供了对人类SAE俱乐部细胞亚群的组成和吸烟诱导的俱乐部细胞生物学变化的见解。
The club cell, a small airway epithelial (SAE) cell, plays a central role in human lung host defense. We hypothesized that subpopulations of club cells with distinct functions may exist. The SAE of healthy nonsmokers and healthy cigarette smokers were evaluated by single-cell RNA sequencing, and unsupervised clustering revealed subpopulations of SCGCB1A1+KRT5loMUC5AC− club cells. Club cell heterogeneity was supported by evaluations of SAE tissue sections, brushed SAE cells, and in vitro air–liquid interface cultures. Three subpopulations included: (1) progenitor; (2) proliferating; and (3) effector club cells. The progenitor club cell population expressed high levels of mitochondrial, ribosomal proteins, and KRT5 relative to other club cell populations and included a differentiation branch point leading to mucous cell production. The small proliferating population expressed high levels of cyclins and proliferation markers. The effector club cell cluster expressed genes related to host defense, xenobiotic metabolism, and barrier functions associated with club cell function. Comparison of smokers vs. nonsmokers demonstrated that smoking limited the extent of differentiation of all three subclusters and altered SAM pointed domain-containing Ets transcription factor (SPDEF)-regulated transcription in the effector cell population leading to a change in the location of the branch point for mucous cell production, a potential explanation for the concomitant reduction in effector club cells and increase in mucous cells in smokers. These observations provide insights into both the makeup of human SAE club cell subpopulations and the smoking-induced changes in club cell biology.
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影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
158.5
作者：
AUERBACH, O;HAMMOND, EC;GARFINKEL, L
通讯作者：
GARFINKEL, L
影响因子：
158.5
作者：
AUERBACH, O;GERE, JB;STOUT, AP
通讯作者：
STOUT, AP
DOI：
10.1164/ajrccm.157.6.9707011
发表时间：
1998-06-01
影响因子：
24.7
作者：
Boers, JE;Ambergen, AW;Thunnissen, FBJM
通讯作者：
Thunnissen, FBJM
DOI：
10.1164/rccm.201911-2199oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
Deprez, Marie;Zaragosi, Laure-Emmanuelle;Barbry, Pascal
通讯作者：
Barbry, Pascal