Transcriptional characterisation of human lung cells identifies novel mesenchymal lineage markers.
Transcriptional characterisation of human lung cells identifies novel mesenchymal lineage markers.
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DOI：
10.1183/13993003.00746-2019
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Al Alam D
中科院分区：
文献类型：
--
作者：
Danopoulos S;Bhattacharya S;Mariani TJ;Al Alam D
肺间充质在成熟的呼吸系统中产生多种不同的细胞谱系，包括气道和脉管系统的平滑肌细胞（SMC）。然而，在人肺的规格和间充质细胞的多样性缺乏透彻的理解。我们完成了胎儿人肺组织的单细胞RNA测序分析。在Seurat中进行典型相关分析、聚类、聚类标记基因鉴定和tSNE表示。使用Toppfun注释细胞群体。免疫组织化学和原位杂交用于验证关键标记基因的时空基因表达模式。我们确定了分子上不同的人口代表“承诺”胎儿人肺内皮细胞，周细胞和平滑肌细胞（SMC）。早期内皮细胞谱系表达"经典"内皮细胞标记物（PECAM、CLND 5），而周细胞表达PDGFR β、THY 1和基底膜分子（COL 4、层粘连蛋白、蛋白聚糖）。我们观察到大量的“非特异性”人肺间充质祖细胞，其特征在于表达COL1和多种弹性蛋白纤维基因（ELN，MFAP2，FBN1）。我们密切关注ACTA 2表达定义的间充质谱系的多样性。两个细胞群体，具有最高水平的ACTA 2转录活性，表达了独特的标记物与气道或血管SMC。这些标记基因的时空分析证实了气道（HHIP，MYLK，IGF1）和血管（NTRK3，MEF2C）SMC在发育中的人肺中的早期和持续的空间特化。我们的数据表明，规范不同的气道和血管SMC表型建立在发展的早期，可以确定使用我们提供的标记物。
The lung mesenchyme gives rise to multiple distinct lineages of cells in the mature respiratory system, including smooth muscle cells (SMCs) of the airway and vasculature. However, a thorough understanding of the specification and mesenchymal cell diversity in the human lung is lacking. We completed single cell RNA sequencing analysis of fetal human lung tissues. Canonical correlation analysis, clustering, cluster marker gene identification and tSNE representation was performed in Seurat. Cell populations were annotated using Toppfun. Immunohistochemistry and in situ hybridization were used to validate spatio-temporal gene expression patterns for key marker genes. We identified molecularly distinct populations representing “committed” fetal human lung endothelial cells, pericytes, and smooth muscle cells (SMCs). Early endothelial lineages expressed “classic” endothelial cell markers (PECAM, CLND5) while pericytes expressed PDGFRβ, THY1 and basement membrane molecules (COL4, laminin, proteoglycans). We observed a large population of “nonspecific” human lung mesenchymal progenitor cells characterized by expression of COL1 and multiple elastin fiber genes (ELN, MFAP2, FBN1). We closely characterized diversity of mesenchymal lineages defined by ACTA2 expression. Two cell populations, with the highest levels of ACTA2 transcriptional activity, expressed unique sets of markers associated with airway- or vascular- SMCs. Spatio-temporal analysis of these marker genes confirmed early and persistent spatial specification of airway (HHIP, MYLK, IGF1) and vascular (NTRK3, MEF2C) SMCs in the developing human lung. Our data suggest that specification of distinct airway and vascular SMC phenotypes are established early in development and can be identified using the markers we provide.
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影响因子：
11.8
作者：
Volckaert T;Yuan T;Chao CM;Bell H;Sitaula A;Szimmtenings L;El Agha E;Chanda D;Majka S;Bellusci S;Thannickal VJ;Fässler R;De Langhe SP
通讯作者：
De Langhe SP
影响因子：
16.6
作者：
Jain, Rajan;Barkauskas, Christina E.;Takeda, Norifumi;Bowie, Emily J.;Aghajanian, Haig;Wang, Qiaohong;Padmanabhan, Arun;Manderfield, Lauren J.;Gupta, Mudit;Li, Deqiang;Li, Li;Trivedi, Chinmay M.;Hogan, Brigid L. M.;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.
DOI：
10.1002/path.5188
发表时间：
2019-03
期刊：
The Journal of pathology
影响因子：
--
作者：
Danopoulos S;Thornton ME;Grubbs BH;Frey MR;Warburton D;Bellusci S;Al Alam D
通讯作者：
Al Alam D
影响因子：
5.5
作者：
Lange, Alexander W.;Sridharan, Anusha;Whitsett, Jeffrey A.
通讯作者：
Whitsett, Jeffrey A.
影响因子：
64.8
作者：
Montoro DT;Haber AL;Biton M;Vinarsky V;Lin B;Birket SE;Yuan F;Chen S;Leung HM;Villoria J;Rogel N;Burgin G;Tsankov AM;Waghray A;Slyper M;Waldman J;Nguyen L;Dionne D;Rozenblatt-Rosen O;Tata PR;Mou H;Shivaraju M;Bihler H;Mense M;Tearney GJ;Rowe SM;Engelhardt JF;Regev A;Rajagopal J
通讯作者：
Rajagopal J