Functional Pdgfra fibroblast heterogeneity in normal and fibrotic mouse lung.
Functional Pdgfra fibroblast heterogeneity in normal and fibrotic mouse lung.
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正常和纤维化小鼠肺功能Pdgfra成纤维细胞异质性。
DOI：
10.1172/jci.insight.164380
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发表时间：
2023-11-22
期刊：
影响因子：
8
通讯作者：
Garantziotis, Stavros
中科院分区：
文献类型：
--
作者：
Trempus, Carol S.;Papas, Brian N.;Sifre, Maria I.;Bortner, Carl D.;Scappini, Erica;Tucker, Charles J.;Xu, Xin;Johnson, Katina L.;Deterding, Leesa J.;Williams, Jason G.;Johnson, Dylan J.;Li, Jian-Liang;Sutton, Deloris;Ganta, Charan;Mahapatra, Debabrata;Arif, Muhammad;Basu, Abhishek;Pommerolle, Lenny;Cinar, Resat;Perl, Anne K.;Garantziotis, Stavros
异常的成纤维细胞功能在特发性肺纤维化的发病机制中起着关键作用，特发性肺纤维化是一种对肺损伤做出反应的持续细胞外基质沉积的毁灭性疾病。血小板衍生生长因子α阳性（Pdgfra+）脂成纤维细胞（LipoFB）对于肺损伤反应和功能性肺泡干细胞生态位的维持至关重要。关于肺损伤对LipoFB功能的影响知之甚少。在这里，我们使用单细胞RNA-Seq（scRNA-Seq）技术和PdgfraGFP谱系追踪来生成博来霉素暴露后14天正常和损伤小鼠肺中Pdgfra+成纤维细胞的转录组学谱，生成根据治疗分离的11个独特的转录组学簇。虽然正常和受伤的LipoFB共享一个共同的基因签名，受伤的LipoFB获得纤维化途径的活性与脂肪生成途径的衰减。在3D类器官模型中，损伤的Pdgfra+成纤维细胞支持的类器官在形态上不同于用正常成纤维细胞培养的类器官，并且scRNA-Seq分析表明由损伤的Pdgfra+成纤维细胞支持的肺泡上皮中的不同转录组学变化。总之，虽然受伤肺部中的LipoFB尚未从其利基中迁移并保留其脂肪生成特性，但它们获得了潜在可逆的纤维化特征，这可能会改变上皮再生的动力学，并可能导致修复失调，从而导致纤维化。
Aberrant fibroblast function plays a key role in the pathogenesis of idiopathic pulmonary fibrosis, a devastating disease of unrelenting extracellular matrix deposition in response to lung injury. Platelet-derived growth factor α–positive (Pdgfra+) lipofibroblasts (LipoFBs) are essential for lung injury response and maintenance of a functional alveolar stem cell niche. Little is known about the effects of lung injury on LipoFB function. Here, we used single-cell RNA-Seq (scRNA-Seq) technology and PdgfraGFP lineage tracing to generate a transcriptomic profile of Pdgfra+ fibroblasts in normal and injured mouse lungs 14 days after bleomycin exposure, generating 11 unique transcriptomic clusters that segregated according to treatment. While normal and injured LipoFBs shared a common gene signature, injured LipoFBs acquired fibrogenic pathway activity with an attenuation of lipogenic pathways. In a 3D organoid model, injured Pdgfra+ fibroblast–supported organoids were morphologically distinct from those cultured with normal fibroblasts, and scRNA-Seq analysis suggested distinct transcriptomic changes in alveolar epithelia supported by injured Pdgfra+ fibroblasts. In summary, while LipoFBs in injured lung have not migrated from their niche and retain their lipogenic identity, they acquire a potentially reversible fibrogenic profile, which may alter the kinetics of epithelial regeneration and potentially contribute to dysregulated repair, leading to fibrosis.
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影响因子：
7.7
作者：
Chanda D;Rehan M;Smith SR;Dsouza KG;Wang Y;Bernard K;Kurundkar D;Memula V;Kojima K;Mobley JA;Benavides GA;Darley-Usmar V;Kim YI;Zmijewski JW;Deshane JS;De Langhe S;Thannickal VJ
通讯作者：
Thannickal VJ
DOI：
10.1073/pnas.0908268106
发表时间：
2009-11-10
影响因子：
11.1
作者：
Horiguchi, Masahito;Inoue, Tadashi;Nakamura, Tomoyuki
通讯作者：
Nakamura, Tomoyuki
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
5.6
作者：
Kendall RT;Feghali-Bostwick CA
通讯作者：
Feghali-Bostwick CA
DOI：
10.1165/rcmb.2013-0310oc
发表时间：
2015-02-01
影响因子：
6.4
作者：
Bauer, Yasmina;Tedrow, John;Kaminski, Naftali
通讯作者：
Kaminski, Naftali