Delineating the dynamic evolution from preneoplasia to invasive lung adenocarcinoma by integrating single-cell RNA sequencing and spatial transcriptomics.
Delineating the dynamic evolution from preneoplasia to invasive lung adenocarcinoma by integrating single-cell RNA sequencing and spatial transcriptomics.
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DOI：
10.1038/s12276-022-00896-9
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发表时间：
2022-11
影响因子：
12.8
通讯作者：
Jiang, Tao
中科院分区：
文献类型：
--
作者：
Zhu, Jianfei;Fan, Yue;Xiong, Yanlu;Wang, Wenchen;Chen, Jiakuan;Xia, Yanmin;Lei, Jie;Gong, Li;Sun, Shiquan;Jiang, Tao
肺腺癌(LUAD)从原位腺癌(AIS)到微侵袭性腺癌(MIA)再到侵袭性腺癌(IAC)的动态和序贯过程中所涉及的细胞生态学和空间生态位尚不清楚。在这里，我们进行了单细胞RNA测序(scRNA-seq)和空间转录(ST)的综合分析，以表征LUAD侵袭轨迹的细胞图谱。我们发现UBE2C + 癌细胞亚群在LUAD的侵袭过程中不断增加，且在IAC中显著升高，其空间分布在IAC的周边癌区域，表现为更恶性的表型。此外，对TME细胞亚群的分析显示，参与侵袭性LUAD整个过程的肥大细胞、单核细胞和淋巴管内皮细胞持续减少，并伴随着从AIS到MIA的NK细胞和MALT B细胞的增加，以及从MIA到IAC的Tregs和分泌型B细胞的增加。值得注意的是，对于AIS，癌细胞、NK细胞和肥大细胞共同定位于癌区；然而，对于IAC，Tregs与癌细胞共同定位。最后，肿瘤细胞与TME细胞之间的通讯和相互作用导致转化生长因子-β信号的结构性激活，参与了IAC的侵袭。因此，我们的结果揭示了癌细胞和TME亚群的特定细胞信息和空间构筑，以及它们之间的细胞相互作用，这将有助于在LUAD从AIS到IAC的侵袭过程中识别和发展精确医学。一张显示肺癌如何从静止性癌发展到浸润性癌的地图可能会为新的治疗方法提供信息。世界卫生组织将肺腺癌定义为三个阶段：首先是原位病变，然后是微创，然后是完全侵袭。关于所涉及的细胞群体及其在癌症发展过程中的位置的细节一直有限。西安空军医科大学的朱建飞、中国和他的同事结合了单细胞核糖核酸测序和空间转录组学的优势，绘制了一张地图，显示不同类型的细胞何时何地参与肺癌的进展。他们表明，UBE2C细胞是众所周知的肿瘤形成细胞，在早期阶段就参与其中，可能是侵袭的关键临床指标。后来，可以抑制身体对肿瘤的免疫反应的调节性T细胞被招募到癌症区域，而其他类型的细胞减少。
The cell ecology and spatial niche implicated in the dynamic and sequential process of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) have not yet been elucidated. Here, we performed an integrative analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to characterize the cell atlas of the invasion trajectory of LUAD. We found that the UBE2C + cancer cell subpopulation constantly increased during the invasive process of LUAD with remarkable elevation in IAC, and its spatial distribution was in the peripheral cancer region of the IAC, representing a more malignant phenotype. Furthermore, analysis of the TME cell type subpopulation showed a constant decrease in mast cells, monocytes, and lymphatic endothelial cells, which were implicated in the whole process of invasive LUAD, accompanied by an increase in NK cells and MALT B cells from AIS to MIA and an increase in Tregs and secretory B cells from MIA to IAC. Notably, for AIS, cancer cells, NK cells, and mast cells were colocalized in the cancer region; however, for IAC, Tregs colocalized with cancer cells. Finally, communication and interaction between cancer cells and TME cell-induced constitutive activation of TGF-β signaling were involved in the invasion of IAC. Therefore, our results reveal the specific cellular information and spatial architecture of cancer cells and TME subpopulations, as well as the cellular interaction between them, which will facilitate the identification and development of precision medicine in the invasive process of LUAD from AIS to IAC. A map showing how lung cancer progresses from static to invasive carcinomas could inform new therapeutic approaches. The World Health Organisation defines three stages of lung adenocarcinoma: first, in situ lesions, then minimally invasive, then fully invasive. Details about the cell populations involved and their locations during cancer development have been limited. Jianfei Zhu at Air Force Medical University in Xi’an, China, and co-workers have combined the strengths of single-cell RNA sequencing and spatial transcriptomics to produce a map showing where and when different cell types become involved in lung cancer progression. They showed that UBE2C cells, well-known tumor-forming cells, are involved at early stages, and could be key clinical indicators of invasion. Later, regulatory T-cells, which can suppress the body’s immune responses to tumors, are recruited into cancer regions while other cell types are reduced.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan
影响因子：
46.9
作者：
Cortal, Akira;Martignetti, Loredana;Rausell, Antonio
通讯作者：
Rausell, Antonio
肺亚实性结节的基因组特征：突变景观和放射学特征
影响因子：
24.3
作者：
Li, Yanmeng;Li, Xiao;Wang, Jun
通讯作者：
Wang, Jun
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne