Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing.
Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing.
复制标题
利用单细胞 RNA 测序破译人肺腺癌的细胞谱系特征
DOI：
10.1038/s41467-021-26770-2
复制
发表时间：
2021-11-11
影响因子：
16.6
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wang Z;Li Z;Zhou K;Wang C;Jiang L;Zhang L;Yang Y;Luo W;Qiao W;Wang G;Ni Y;Dai S;Guo T;Ji G;Xu M;Liu Y;Su Z;Che G;Li W
肺腺癌（LUAD）由癌前病变如非典型腺瘤样增生发展而来，后者依次进展为原位腺癌和微浸润性腺癌，最终发展为浸润性腺癌。这种逐步进展背后的细胞异质性和分子事件仍不清楚。在这项研究中，我们对从25例处于肺腺癌四个组织学阶段的患者中收集的268,471个细胞进行了单细胞RNA测序，并将它们与正常细胞类型进行比较。我们检测到一组与2型肺泡细胞（AT2）非常相似的细胞，它们在非典型腺瘤样增生期间出现，并且随着肺腺癌的进展，其转录谱开始与AT2细胞的转录谱出现差异，呈现出干细胞样细胞的特征。我们确定了与能量代谢和核糖体合成相关的基因，这些基因在肺腺癌的早期阶段上调，并可能促进疾病进展。中期因子（MDK）和金属蛋白酶组织抑制因子1（TIMP1）可能是了解肺腺癌发病机制的潜在生物标志物。我们的工作揭示了肺腺癌进展不同组织学阶段潜在的转录特征，我们的发现可能有助于早期诊断。
肺腺癌的起源和进展仍知之甚少。在这里，作者利用单细胞RNA测序和多重成像分析了患者样本中肺腺癌的组成和进展，揭示了与2型肺泡细胞潜在的转录差异。
Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis.
登录
查看更多内容
影响因子：
23.9
作者：
Dost AFM;Moye AL;Vedaie M;Tran LM;Fung E;Heinze D;Villacorta-Martin C;Huang J;Hekman R;Kwan JH;Blum BC;Louie SM;Rowbotham SP;Sainz de Aja J;Piper ME;Bhetariya PJ;Bronson RT;Emili A;Mostoslavsky G;Fishbein GA;Wallace WD;Krysan K;Dubinett SM;Yanagawa J;Kotton DN;Kim CF
通讯作者：
Kim CF
影响因子：
16.6
作者：
Gong L;Kwong DL;Dai W;Wu P;Li S;Yan Q;Zhang Y;Zhang B;Fang X;Liu L;Luo M;Liu B;Chow LK;Chen Q;Huang J;Lee VH;Lam KO;Lo AW;Chen Z;Wang Y;Lee AW;Guan XY
通讯作者：
Guan XY
影响因子：
8
作者：
Cheung WK;Nguyen DX
通讯作者：
Nguyen DX
影响因子：
5.6
作者：
Inamura K
通讯作者：
Inamura K
影响因子：
16.6
作者：
Angelidis, Ilias;Simon, Lukas M.;Schiller, Herbert B.
通讯作者：
Schiller, Herbert B.