Single-cell transcriptome profiling reveals the mechanism of abnormal proliferation of epithelial cells in congenital cystic adenomatoid malformation.
Single-cell transcriptome profiling reveals the mechanism of abnormal proliferation of epithelial cells in congenital cystic adenomatoid malformation.
复制标题
单细胞转录组分析揭示了先天性囊性腺瘤样畸形中上皮细胞异常增殖的机制。
DOI：
10.1016/j.yexcr.2020.112299
复制
发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Zhang S;Ye C;Xiao J;Yang J;Zhu C;Xiao Y;Ye M;Chen Q
目的先天性囊性腺瘤样畸形（CCAM）是最常见的先天性肺畸形，病因不明。本研究采用单细胞RNA测序（scRNA-seq）技术对CCAM的细胞结构进行了分析，并对CCAM相关的细胞和分子事件进行了研究。损伤和非损伤区域的样品在手术过程中收集scRNA-seq.ResultsIn总数，19,904个细胞获得的中位数UMI计数为7032每个细胞和1995个中位数基因每个细胞。病变区和非病变区上皮细胞分别占27.23%和17.85%，间充质细胞分别占2.67%和16.06%（P < 0.0001）。进一步的上皮细胞聚类显示肺泡1型细胞的分数（AT 1，N：23.65%; L：49.81%）、AT 2在病变样本中，club-1（N：9.02%; L：17.57%）、club-3（N：1.18%; L：4.15%）和基底细胞（N：0.34%; L：2.93%）增加（P < 0.0001）。假时间轨迹分析显示club-1/基底细胞→ AT 2 →club-3→ AT 1和club-1，2/基底细胞→ AT 2的轨迹。肥大细胞（N：0.63%; L：结论CCAM患者AT 1、AT 2、club-1/3和基底细胞增多，新定义的club-1/3和基底细胞可能是AT 1和AT 2细胞增殖的来源。肥大细胞的增加可能通过CD 44与HBEGF和FGFR 2的相互作用促进上皮细胞增殖。
ObjectivesCongenital cystic adenomatoid malformation (CCAM) is the most common congenital pulmonary anomaly with unknown etiology. Here, single-cell RNA sequencing (scRNA-seq) was used to map its cellular landscape and identify the underlying cellular and molecular events related to CCAM.MethodsThis study involved a 4.25 year old patient with grade Ⅱ–Ⅲ CCAM at the Children's Hospital of Fudan University. Samples of lesioned and non-lesioned areas were collected during surgery for scRNA-seq.ResultsIn total, 19,904 cells were obtained with median UMI counts of 7032 per cell and 1995 median genes per cell. In terms of lesioned and non-lesioned areas, epithelial cells accounted for 27.23% and 17.85%, respectively, while mesenchymal cells accounted for 2.67% and 16.06%, respectively (P < 0.0001). Further clustering of epithelial cells revealed that the fractions of alveolar type 1 cells (AT1, N: 23.65%; L: 49.81%), AT2(N: 2.02%; L: 5.26%), club-1(N: 9.02%; L: 17.57%), club-3(N: 1.18%; L: 4.15%), and basal cells (N: 0.34%; L: 2.93%) were increased in lesioned samples (P < 0.0001). Pseudotime trajectory analysis showed tracks of club-1/basal cells→AT2→club-3→AT1 and club-1,2/basal→AT2. Mast cells (N: 0.63%; L: 2.48%) were also increased in lesioned samples and interactions ofCD44withHBEGFand FGFR2 were detected between mast and epithelial cells.ConclusionsAT1, AT2, club, and basal cells were increased in CCAM patients, and newly defined club-1/3 and basal cells might be the origin of proliferating AT1 and AT2 cells. Increased mast cells might promote epithelial cell proliferation through interactions of CD44 with HBEGF and FGFR2.
登录
查看更多内容
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
谱系阴性祖细胞大受伤后动员肺上皮。
影响因子：
64.8
作者：
Vaughan, Andrew E.;Brumwell, Alexis N.;Xi, Ying;Gotts, Jeffrey E.;Brownfield, Doug G.;Treutlein, Barbara;Tan, Kevin;Tan, Victor;Liu, Feng Chun;Looney, Mark R.;Matthay, Michael A.;Rock, Jason R.;Chapman, Harold A.
通讯作者：
Chapman, Harold A.
影响因子：
64.8
作者：
Zacharias WJ;Frank DB;Zepp JA;Morley MP;Alkhaleel FA;Kong J;Zhou S;Cantu E;Morrisey EE
通讯作者：
Morrisey EE
影响因子：
1.7
作者：
John A. Bevan;Gabor Kaley;Sukhamay Lahiri;Claude Gaultier;Martin Post
通讯作者：
John A. Bevan;Gabor Kaley;Sukhamay Lahiri;Claude Gaultier;Martin Post
DOI：
10.4067/s0370-41062018000200224
发表时间：
2018-04
期刊：
Revista chilena de pediatria
影响因子：
--
作者：
Margarita Gallardo A;Margarita Álvarez de la Rosa R;José F De Luis E;Lorena Mendoza R;Ana Isabel Padilla P;Juan Troyano L
通讯作者：
Margarita Gallardo A;Margarita Álvarez de la Rosa R;José F De Luis E;Lorena Mendoza R;Ana Isabel Padilla P;Juan Troyano L