Understanding tumor ecosystems by single-cell sequencing: promises and limitations

Ren, Xianwen; Kang, Boxi; Zhang, Zemin

doi:10.1186/s13059-018-1593-z

Cited by 174 publications

(122 citation statements)

References 210 publications

(221 reference statements)

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“…The utility of this strategy has been widely shown in many tumor types and the quantification of CTCs can be used as a prognostic factor [45]. Whereas many authors claim that CTCs recapitulate intratumor diversity perfectly, others have reported that they resemble metastasis more than primary tumors [46].…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies

2020

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Effective cancer treatment has been precluded by the presence of various forms of intratumoral complexity that drive treatment resistance and metastasis. Recent single-cell sequencing technologies are significantly facilitating the characterization of tumor internal architecture during disease progression. New applications and advances occurring at a fast pace predict an imminent broad application of these technologies in many research areas. As occurred with next-generation sequencing (NGS) technologies, once applied to clinical samples across tumor types, single-cell sequencing technologies could trigger an exponential increase in knowledge of the molecular pathways involved in cancer progression and contribute to the improvement of cancer treatment. Multifaceted Heterogeneity and Its Impact on Cancer ProgressionTumors comprise various cell populations in constant evolution. Some of this complex heterogeneity derives from genetic diversification and Darwinian selection of tumor cells as they adapt to variable environments. Next-generation sequencing (NGS; see Glossary) used for the past decade had enough sensitivity to detect mutations present in minor cell populations and, combined with multisampling of human tumors (multisampling sequencing), fostered many studies that characterized intratumor heterogeneity in various cancers [1]. The level of intratumor heterogeneity is considered a main driver of therapy resistance and metastasis and is associated with poor prognosis [2].In addition, human cancers frequently have tumor cell populations with different transcriptional programs. This functional diversity is likely associated with the genetic heterogeneity described above but is also the result of many other factors. First, the presence of a hierarchical structure, where a group of quiescent stem-like cells fosters the growth of a tumor comprising cells in different differentiation states, was demonstrated in various tumor types [3]. Additionally, different transcriptional programs can be activated in tumor cells as a response to stochastic factors or to a variable tumor microenvironment. This functional diversity provides tumors with a plasticity that grants a high capacity for adaptation [4].Finally, human tumors comprise not only malignant/transformed cells but also a plethora of different cell types recruited from the surrounding tissue and the immune system. The tumor microenvironment shows also genetic and transcriptional diversity and plays important roles in tumor progression, metastasis, and treatment resistance [1,5].Fine characterization of these levels of tumor heterogeneity is essential to the successful treatment of cancer patients. The recent development of technologies based on sequencing individual cells (single-cell sequencing technologies) opens new ways for the characterization of tumor heterogeneity. At the genetic level, single-cell DNA-seq technologies offer higher sensitivity in the detection of minority clones, the reconstruction of clone structure, and the identification of concurrent ...

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Section: Circulating Tumor Cellsmentioning

confidence: 99%

Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies

2020

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“…Single‐cell transcriptome sequencing (scRNA‐seq) has opened new avenues for the understanding of the biological role of cell populations, their origins, and interactions (Ren et al , 2018). Single‐cell approaches – in contrast to bulk tissue sequencing – allow to determine which cell type is responsible for transcriptomic changes, which is of fundamental importance for the understanding of tumor biology.…”

Section: Introductionmentioning

confidence: 99%

Cell type‐specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics

et al. 2020

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As a proof of concept, we profiled tumor samples of nine patients and explored expression differences in the three cell populations between tumor and normal tissue. Interestingly, we found that angiogenesis-related genes were upregulated in fibroblasts isolated from tumors compared with normal tissue. Overall, we suggest our protocol as a complementary and more scalable approach compared with single-cell RNA sequencing to investigate associations between clinical parameters and transcriptomic alterations of specific cell populations in esophageal adenocarcinoma.

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“…Recent advances in cancer immunotherapies have provided paradigm shifts in treating patients with advanced malignancies. The development and therapeutic use of various immunotherapy regimens rely on the systems‐level understanding of cellular composition, interaction, and dynamics of the tumor ecosystem . Tumors are infiltrated with immune, stromal, and other cell types, leading to extraordinary intratumor heterogeneity, which plays a vital role in tumor progression and requires new methods such as single‐cell multiomics approaches and systems‐level analysis to tackle.…”

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confidence: 99%