Integrating microarray-based spatial transcriptomics and single-cell RNA-sequencing reveals tissue architecture in esophageal squamous cell carcinoma

Guo, Wei; Zhou, Bolun; Yang, Zhenlin; Liu, Xiang; Huai, Qilin; Guo, Lei; Xue, Xuemin; Tan, Fengwei; Li, Yin; Xue, Qi; Gao, Shugeng; He, Jie

doi:10.1016/j.ebiom.2022.104281

Cited by 28 publications

(16 citation statements)

References 47 publications

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“…The immunofluorescence (IF) staining protocol employed in this study is consistent with the methodology described by Guo et al [ 16 ]. The primary antibodies used were Anti-c-Fos Rabbit pAb (Servicebio, GB11069) and Anti-Cytokeratin 8 Rabbit pAb (Servicebio, GB11231).…”

Section: Methodsmentioning

confidence: 87%

“…Spatial transcriptomic (ST) technology, capable of providing a comprehensive spatial gene expression landscape within the architecture of an entire tissue section [ 13 – 15 ], can effectively overcome this limitation. When integrated with single-cell RNA-sequencing (scRNA-seq) technology, it enables the characterization of cellular alterations in tissue structure and facilitates the elucidation of functional linkage between distinct cell clusters and histological structures [ 15 , 16 ]. Therefore, by integrating these two technologies, we intended to provide a comprehensive understanding of the alterations in epithelial cells and their functions by mimicking the process of proliferative nodular formation in BPH.…”

Section: Introductionmentioning

confidence: 99%

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Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

Fei,

Liu,

et al. 2024

J Transl Med

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Objective Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients. Methods The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification. Results The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers. Conclusions This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

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Section: Methodsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

Fei,

Liu,

et al. 2024

J Transl Med

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“…Also, the emergence of tumor-agnostic treatments and similar immunotherapy-based approaches require such spatial information [41]. As exemplified by combining scRNA-seq with microarray-based spatial transcriptomics, overlaying single-cell data in a spatial context within the tissue can provide unique insights into intervention [44]. Layering bioinformatic tools such as SpaRx on RNA profiles of pharmacogenomic data can potentially predict the heterogeneity in drug responses [45 ▪ ].…”

Section: Translational Levels and The Depth Of Profilingmentioning

confidence: 99%

Explore & actuate: the future of personalized medicine in oncology through emerging technologies

Babu,

Sen

2024

Current Opinion in Oncology

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Purpose of review The future of medicine is aimed to equip the physician with tools to assess the individual health of the patient for the uniqueness of the disease that separates it from the rest. The integration of omics technologies into clinical practice, reviewed here, would open new avenues for addressing the spatial and temporal heterogeneity of cancer. The rising cancer burden patiently awaits the advent of such an approach to personalized medicine for routine clinical settings. Recent findings To weigh the translational potential, multiple technologies were categorized based on the extractable information from the different types of samples used, to the various omic-levels of molecular information that each technology has been able to advance over the last 2 years. This review uses a multifaceted classification that helps to assess translational potential in a meaningful way toward clinical adaptation. Summary The importance of distinguishing technologies based on the flow of information from exploration to actuation puts forth a framework that allows the clinicians to better adapt a chosen technology or use them in combination to enhance their goals toward personalized medicine.

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“…Numerous studies have shown that the in ltration of immune cells, such as T lymphocytes and macrophages, is directly related to patient's response to anti-tumor immunity and immune checkpoint blockade (ICB). 8,9 Neoadjuvant therapies are able to modify the anti-tumor response of ICB by modulating the immune microenvironment phenotype. 10 For example, tumors of the immune-enriched signature exhibited more pathological tumor regression.…”

Section: Introductionmentioning

confidence: 99%

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Zheng,

Li,

Yuan

et al. 2024

Preprint

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Background: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. Patients and methods: A total of 41 patients with locally advanced ESCC were recruited. Paired matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. Results: The differences of immune cell patterns before and after treatment were investigated, using matched paired tissues of 41 patients who received R0 resection. In the pretreatment tissues, more stromal CD3+FoxP3+ Tregs and CD86+/CD163+ macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with pCR patients. Spatial analyses showed majority of macrophages were mainly distributed in close proximity to tumor nest in pN1 patients. In the posttreatment tissues, pCR patients had less CD86+ cells infiltration, whereas higher CD86+ cell densities were significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous tumor-associated immune cell patterns were found. Upon to the treatment, CD3+ T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCRs. In contrast, a noticeable increase and a less obvious decrease of CD86+ cell infiltration was depicted in non-pCRs and pCRs, respectively. Furthermore, opposite trends of the treatment-induced alterations of CD8+ and CD15+ cells were observed between pN0 and pN1 patients. Conclusions: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy, and therefore provide rationale for the further improvement of neoadjuvant therapy in ESCC.

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Integrating microarray-based spatial transcriptomics and single-cell RNA-sequencing reveals tissue architecture in esophageal squamous cell carcinoma

Cited by 28 publications

References 47 publications

Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

Explore & actuate: the future of personalized medicine in oncology through emerging technologies

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

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