基于单细胞RNA测序的急性髓系白血病细胞和分子特征研究。

IF 6 2区 医学 Q1 ONCOLOGY
Zheng-Fa Li, Jun-Rong Lu, Yun Dai, Rui-Jiao Mao, Yang-Liu Lu, Rong Sun, Jiao Liu, Lu-Lu Dong, Li-Ling Xia, Yun-Chao Xu, Tian Xia, Xiao Qin, Ting Dong
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引用次数: 0

摘要

急性髓系白血病(AML)是一种由未成熟髓系造血干细胞引起的高度异质性克隆性恶性疾病。本研究的目的是通过对单细胞测序数据的分析,鉴定AML的主要细胞簇及其相关中枢基因。我们从5名AML患者和3名对照患者的骨髓样本中获得了58,717个细胞和27,311个基因的全面和有价值的景观。然后,鉴定出9个细胞亚群。在AML和对照组中,共同髓系祖细胞(CMP)、髓细胞和前髓细胞的比例有显著差异,因为这些细胞在本研究中被用作分化细胞。在数据合并和去权重后,共鉴定出26个差异表达基因。选取ELANE、LTF、S100A12和SLPI 4个枢纽基因进行进一步分析。对髓细胞和前髓细胞进行均匀性分析,随后将其重新聚集成11个和8个细胞簇。综上所述,我们利用高通量单细胞转录组学分析了AML患者骨髓中的细胞景观,发现了髓细胞、前髓细胞及相关中枢基因ELANE、LTF、S100A12、SLPI 2种关键细胞类型,并揭示了这些关键细胞的生物学功能、调控关系、发育状态,以及中枢基因所涉及的生物学途径、分子调控机制和相关药物。我们的数据和发现为AML的病理发展提供了新的见解,并可以在AML的治疗中得到启发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cellular and molecular features of acute myeloid leukemia investigation based on single-cell RNA sequencing.

Acute myeloid leukemia (AML) is defined as a highly heterogeneous clonal malignant disease of immature myeloid hematopoietic stem cells. The objective of this study was to identify the principal cell clusters in AML and their associated hub genes through the analysis of single-cell sequencing data. We present a comprehensive and valuable landscape of 58,717 cells and 27,311 genes derived from bone marrow samples obtained from 5 patients with AML and 3 controls. Then, 9 cell subclusters were identified. The ratios of common myeloid progenitor (CMP), Myelocyte, and Pro-Myelocyte were found to be significantly different between AML and control, as these cells were utilized as differential cells in the present study. A total of 26 differentially expressed genes were identified following the merging and de-weighting of the data. 4 hub genes, ELANE, LTF, S100A12, and SLPI, were selected for further analysis. Homogeneity analysis was conducted on the Myelocyte and Pro-Myelocyte cells, which were subsequently re-clustered into 11 and 8 cell clusters, respectively. In conclusion, we leveraged high-throughput single-cell transcriptomics to parse the cell landscape in the bone marrow from AML patients, 2 key cell types, myelocyte, and pro-myelocyte and related hub genes, ELANE, LTF, S100A12, SLPI were found, and biological functions, regulatory relationships, and developmental status of these key cells, as well as the biological pathways, the molecular regulatory mechanisms, and the related drugs, involved in the hub genes were demonstrated. Our data and findings provide novel insight into AML pathological development and can be inspired in the treatment of AML.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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