Ready for your all-in-one single cell sequencing solution?
Contact us

Annual Research Roundup: 2023’s Most Impactful Publications!

6’
Immunology Oncology Review

2023 was a busy and successful year for our scientific community. There are now over 200 publications from researchers using Singleron’s products and we would like to congratulate every single one of these thriving scientists on their achievements and contributions to the world’s understanding of diseases and molecular mechanisms.

As 2023 comes to an end, it is time to look back at some of the most impactful publications from this year:

Novel immunotherapeutic target identified in pancreatic cancer (Sang W. et al., Cancer Discov. 2023; Werba G. et al., Nat. Comm. 2023):

Did you know that pancreatic ductal adenocarcinoma (PDAC) patients have a survival rate of only 11%? This is due to very limited effectiveness of drugs and underlines the importance for novel approaches and advances in this field. Sang et al. identified RIPK2 as a crucial driver of immune evasion of cytotoxic T-cell killing through an in vivo CRISPR screen. To then understand how RIPK2 depletion manipulates the tumor microenvironment, scRNA sequencing was performed. This allowed the authors to map the tumor-immune transcriptional landscape of tumor-infiltrating CD45+ leukocytes from KPCmut tumors. In a second publication focusing more on the effects of chemotherapy on pancreatic tumor and its microenvironment, NYU Pancreatic Cancer Center scientist Werba G. and his colleagues reported earlier this year that chemotherapy profoundly impacts the PDAC tumor microenvironment and may promote resistance to immunotherapy.

Figure 1: Single-cell analysis reveals the transcriptomic landscape in PDAC. A) Clinicopathologic characteristics for each patient sample including treatment status, stage, Moffitt subtype, and procedure. EUS endoscopic ultrasound. B) Workflow depicting sample acquisition, processing, and analysis. Designed with BioRender©. C) UMAP, embedding of the expression profile of 139,446 cells that passed quality control from n = 27 patient samples. Distinct clusters are annotated and color-coded. CAF cancer-associated fibroblast, NK natural killer, UMAP uniform manifold approximation and projection. (Werba G. et al., Nat. Comm., 2023) Licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/).

Developments in understanding rare but aggressive male breast cancer (Sun H et al., Nat. Commun., 2023):

Rare? Yes! Nevertheless important? Absolutely! Breast cancer is the most common cancer among women, but rare among men. Sun H. and his team from Nanjing Medical University employed scRNA-seq and scTCR-seq technology to investigate the tumor microenvironment of male- and female breast cancer samples. Analysis of 111,038 single cells revealed differences in immune infiltration and cellular metabolism. Particularly, the researchers found lower T cell infiltration and higher metastasis-related activities in male breast cancer, along with distinctive T cell activation patterns and cancer cell – immune cell interactions, providing crucial insights into the tumor immunology and metabolism of male breast cancer.

Figure 2: Characterization of subpopulations and clone sizes of T cells in male- and female breast cancer samples based on scRNA-seq and scTCR-seq. A) UMAP plot showing the subpopulations of T cells. B) Heatmap showing the odds ratio of each T cell subpopulation calculated by Fisher’s exact test. *P < 0.05; **P < 0.01. Red color represents subpopulations enriched in MBC samples, and blue color represents subpopulations enriched in FBC samples. C) UMAP plot showing the clone sizes of T cells in male breast cancer (left) and female breast cancer (right) samples. (Sun H et al., Nat. Commun., 2023). Licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/).

Insights into mechanisms of progressive muscle disorders through single nuclei sequencing (Nelke C. et al., Acta Neuropathol., 2023)

Inclusion Body Myositis (IBM) ranks as the most common type of inflammatory myopathy in adults over the age of 50. Muscle inflammation, weakness, and atrophy are typical for this neuromuscular disease that currently lacks effective therapeutic approaches. Nelke C. and his colleagues from Germany studied the muscle-resident cell populations of IBM patients as potential driver of disease compared to non-diseased controls and immune-mediated necrotizing myopathy patients. Single nuclei transcriptomics revealed a specific cluster of fibro-adipogenic progenitors (FAPs) in IBM muscle cells, displaying senescence characteristics like a pro-inflammatory secretome, p21 expression, and increased β-galactosidase activity. The report highlights the altered phenotypical landscape of muscle-resident cells in IBM, demonstrating that FAPs, not myofibers, are the primary senescent cell type, potentially impacting muscle health and structural integrity.

Figure 3: Single-nuclei RNA sequencing of IBM and NDC muscle. A total of 6 frozen muscle specimens were processed for single nuclei-RNAseq (3 samples per group). A total of ~ 30,000 nuclei were included for downstream processing and clustering after quality control. A) UMAP embedding demonstrating distinct clusters of cell types and subtypes. B) Clustered dot plot visualization of top-regulated marker genes. The mean expression for each cluster is indicated by color code. The dot size indicates the percent of expressing cells. Clusters were annotated based on marker genes. Nelke C. et al., Acta Neuropathol., 2023) Licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/).

News from the world of immunology and HSC research (Wang J et al., Blood ,2023):

Chronic active Epstein-Barr Virus (EBV) infection can be a life-threatening disease due to persisting infection. While EBV is observed in multiple hematopoietic lineages upon diagnosis, its origins remained elusive. To interrogate this, Wang J. et al. performed single cell RNA sequencing of bone marrow and peripheral blood samples from Chronic Active Epstein-Bass Virus (CAEBV) patients and healthy controls. Using Singleron’s FocuSCOPE Kit allowed them to simultaneous sequence the whole transcriptome and detect predefined target sequences, in this case EBV-specific transcripts, at single cell resolution. The scRNA sequencing revealed presence of EBV-infected hematopoietic stem cells (HSCs) that showed increased differentiation. Furthermore, the infection impacted both the innate and adaptive immune system, resulting in inflammatory responses. These novel insights into mechanisms of disease build ground for developing innovative therapy strategies for CAEBV.

These publications are just a few selected from many more highly valuable contributions to the current knowledge of humankind. We are thrilled to see our various single-cell technologies in action and can’t wait to see what milestones the next year holds.

References:

Wenhua Sang, Yiduo Zhou, Haiyan Chen, Chengxuan YU, Lisi Dai, Zhongkun Liu, Lang Chen, Yimin Fang, Panpan Ma, Xiangji Wu, Hao Kong, Wenting Liao, Hong Jiang, Junbin Qian, Da Wang, Yun-Hua Liu; Receptor-interacting protein kinase 2 is an immunotherapy target in pancreatic cancer. Cancer Discov 2023; https://doi.org/10.1158/2159-8290.CD-23-0584

Werba, G., Weissinger, D., Kawaler, E.A. et al. Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment. Nat Commun 14, 797 (2023). https://doi.org/10.1038/s41467-023-36296-4

Sun, H., Zhang, L., Wang, Z. et al. Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer. Nat Commun 14, 5590 (2023). https://doi.org/10.1038/s41467-023-41318-2

Nelke, C., Schroeter, C.B., Theissen, L. et al. Senescent fibro-adipogenic progenitors are potential drivers of pathology in inclusion body myositis. Acta Neuropathol 146, 725–745 (2023). https://doi.org/10.1007/s00401-023-02637-2

Jingshi Wang, Min Su, Na Wei, Huanyu Yan, Jia Zhang, Yi Gong, Lin Wu, Dina Suolitiken, Yubo Pi, Deli Song, Leilei Chen, Huan Liu, Shuo Yang, Xi Wang, Zhao Wang; Chronic Active Epstein-Barr Virus Disease Originates from Infected Hematopoietic Stem Cells. Blood 2023; blood.2023021074. doi: https://doi.org/10.1182/blood.2023021074

A post by Samantha Langer

Check out our latests blog posts

Learn more