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

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.

• Authors: 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, Weimin Li
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 6500 (11 11 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34764257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• MDK protein, human
• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Midkine

Topics

• Adenocarcinoma of Lung (genetics, metabolism)
• Cell Lineage
• Energy Metabolism (genetics, physiology)
• Humans
• Lung Neoplasms (genetics, metabolism)
• Midkine (genetics, metabolism)
• Ribosomes (genetics, metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)