Single‐cell RNA sequencing analysis reveals transcriptional heterogeneity of multiple primary lung cancer

Abstract

IntroductionWith the advancements in early diagnosis, more and more patients with multiple primary lung cancer (MPLC) have been identified. However, the progression of MPLC involves complex changes in cell composition and metabolic function, which remains largely controversial.ObjectiveOur study aims to comprehensively reveal the cellular characteristics and inter‐cellular connections of MPLC.MethodsWe performed scRNA‐seq from 23 samples of six MPLC patients, combined with bulk whole‐exome sequencing. We performed trajectory analysis to investigate the transition of different cell types during the development of MPLC.ResultsA total of 1 67 397 cells were sequenced derived from tumour and adjacent tissues of MPLC patients, and tumour, normal, immune and stromal cells were identified. Two states of epithelial cells were identified, which were associated with immune response and cell death, respectively. Furthermore, both CD8+ naïve and memory T cells participated in the differentiation of CD8+ T cells. The terminal states of CD8+ T cells were exhausted T cells and cytotoxic T cells, which positively regulated cell death and were implicated in the regulation of cytokine production, respectively. Two main subpopulations of B cells with distinct functions were identified, which participate in the regulation of the immune response and antigen presentation, respectively. In addition, we found a specific type of endothelial cells that were abundant in tumour samples, with an increasing trend from normal to tumour samples.ConclusionsOur study showed the comprehensive landscape of different cells of MPLC, which might reveal the key cellular mechanisms and, therefore, may provide new insights into the early diagnosis and treatment of MPLC.

Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

“…10,11 As a result, a variety of chromatin modifications, including methylation, acetylation, phosphorylation, ubiquitination, glycosylation and glutarylation, collectively contribute to distinct configurations that impact the efficacy of transcriptional machinery. [12][13][14] Significantly, the disturbance of epigenetic alterations and metabolic pathways is frequently linked to various illnesses, and the interaction between metabolism and chromatin presents numerous prospects for therapeutic interventions. 15,16 Recognising the interaction between metabolic remodelling and dynamic histone tuning is of utmost importance as it is currently in its early stages.…”

“…The alterations, which have the ability to be passed down and undone, have a significant impact on the specific control of cellular characteristics 10,11 . As a result, a variety of chromatin modifications, including methylation, acetylation, phosphorylation, ubiquitination, glycosylation and glutarylation, collectively contribute to distinct configurations that impact the efficacy of transcriptional machinery 12–14 . Significantly, the disturbance of epigenetic alterations and metabolic pathways is frequently linked to various illnesses, and the interaction between metabolism and chromatin presents numerous prospects for therapeutic interventions 15,16 …”

Genomic characteristics and immune landscape of super multiple primary lung cancer

“… 9 Studies have suggested that IAC originates from AAH, and the intermediate states are AIS and MIA during the evolutionary process. 10 , 11 Because of the similar genetic and environmental factors within the same patient, the pathogenesis and progression patterns of different lesions may be similar as well. Thus, exploring the molecular characteristics of lesions at different stages in the same patient can simulate the development process of a single lesion and elucidate the pathogenesis of super MPLC.…”

Single‐cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy

“…This approach has advanced rapidly with diverse methods and platforms such as Smart‐seq, Drop‐seq, Microwell‐seq, etc., 11 providing unprecedentedly deep insights into the complex processes involved in development, physiology and disease. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 In 2015, Macosko et al. 23 first applied scRNA‐seq in ophthalmology to create a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes in the mouse retina.…”

“…Single‐cell RNA sequencing (scRNA‐seq), a novel technology invented by Tang et al., 10 allows high‐throughput molecular profiling of cells across different modalities. This approach has advanced rapidly with diverse methods and platforms such as Smart‐seq, Drop‐seq, Microwell‐seq, etc., 11 providing unprecedentedly deep insights into the complex processes involved in development, physiology and disease 12–22 . In 2015, Macosko et al 23 .…”