Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Zhoufeng Wang, Zhe Li, Kun Zhou, Chengdi Wang, Lili Jiang, Li Zhang, Ying Yang, Wenxin Luo, Wenliang Qiao, Gang Wang, Yinyun Ni, Shuiping Dai, Tingting Guo, Guiyi Ji, Minjie Xu, Yiying Liu, Zhixi Su, Guowei Che () and Weimin Li ()
Additional contact information
Zhoufeng Wang: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Zhe Li: Singlera Genomics Ltd
Kun Zhou: The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
Chengdi Wang: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Lili Jiang: West China Hospital of Sichuan University
Li Zhang: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Ying Yang: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Wenxin Luo: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Wenliang Qiao: Lung Cancer Center, West China Hospital Sichuan University
Gang Wang: Precision Medicine Research Center, West China Hospital, Sichuan University
Yinyun Ni: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Shuiping Dai: West China Hospital, Sichuan University
Tingting Guo: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University
Guiyi Ji: Health Management Center, West China Hospital, Sichuan University
Minjie Xu: Singlera Genomics Ltd
Yiying Liu: Singlera Genomics Ltd
Zhixi Su: Singlera Genomics Ltd
Guowei Che: West China Hospital, Sichuan University
Weimin Li: Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-26770-2

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