Three new articles in the Special Issue “Single-Cell and Spatially Resolved Omics - I” of Journal of Pharmaceutical Analysis Articles describe how single-cell and spatially resolved omics can identify novel therapeutic targets

Single-cell and spatially resolved omics are emerging and rapidly evolving fields of biology and medicine. By allowing us to analyze gene expression at the single-cell level, these methods are contributing to groundbreaking discoveries and insights across multiple disciplines, including neuroscience, immunology, and cancer research. The latest Special Issue of JPA features three articles showcasing tremendous advances and potential of these approaches for uncovering novel biological insights and informing the development of novel therapeutics.

The first study investigated the potential of cannabidiol (CBD), a compound found in the cannabis plant, for the treatment of colorectal tumors. The article was available online in April 2023 and published in Volume 13, Issue 7 of the journal in July 2023. The researchers treated colon cancer cell lines and colon cancer xenograft mice (C57BL/6) with CBD and used single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing to observe the changes. They found that treatment with CBD led to the rewiring of the tumor microenvironment through the alteration of the metabolic patterns of macrophages and anti-tumor signaling pathways. By changing the balance between M2-like and M1-like macrophages, CBD restored the intrinsic anti-tumor properties of the immune system, enhancing the response of the body to anti-programmed cell death protein-1 (PD-1) immunotherapy. “Our study provides new insights into the anti-tumor effects of CBD, which might be a theoretical basis for the future application of cannabinoids in the anti-tumor market,” remarks author Dr. Yang Sung.

In the second study, published in the same Special Issue of JPA, scientists sought to gain insights into the pathogenic mechanisms of chronic dry skin diseases. To this end, they employed scRNA-seq to study the transcriptomic changes in a dry skin mouse model (acetone/ether/water (AEW)-treated model). The sequencing data revealed substantial keratinocyte (skin cell) heterogeneity in dry skin mice and, most importantly, elevated levels of the transcription factor (TF) CUT-like homeobox 1 (Cux1). This led to hyperproliferation of basal cells and keratinocytes, a finding that was also confirmed in skin samples from psoriasis patients with epidermal hyperplasia. “Cux1 could be used as a potential therapeutic target to develop drugs against dry skin-related dermatoses like psoriasis and atopic dermatitis,” comments author Dr. Wei Yang.

Finally, in the third study, also published in this Special Issue in July 2023, researchers investigated the link between microglia communication and Alzheimer’s disease (AD) progression using a mouse AD model and scRNA-seq. They found that an increased percentage of microglia in aging and AD mice, and blood-brain barrier injury may also have contributed to this increase. Interestingly, the interaction strength among microglial subtypes becomes weaker with aging, and amyloid precursor protein (APP) and colony stimulating factor (CSF) drive the occurrence of AD. The author, Dr. Xiaorui Cheng, states: “Exploring the potential pathogenesis of AD could provide a basis for its prevention and treatment, helping reduce its incidence in the future.”

These studies offer hope that further research using single-cell and spatially resolved omics would ultimately lead to treatments for challenging diseases.

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Reference

DOI: https://doi.org/10.1016/j.jpha.2023.04.013

Authors: Xiaofan Sun^1,2, Lisha Zhou², Yi Wang³, Guoliang Deng², Xinran Cao², Bowen Ke⁴, Xiaoqi Wu⁵, Yanhong Gu⁶, Haibo Cheng⁷, Qiang Xu², Qianming Du^8,9, Hongqi Chen¹⁰, and Yang Sun^1,2,11

Affiliations      

¹Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University

²State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University

³Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

⁴Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University

⁵Genergy Bio-technology (Shanghai) Co., Ltd.

⁶The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

⁷Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, The First Clinical College of Nanjing University of Chinese Medicine

⁸General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University

⁹School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University

¹⁰Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

¹¹Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University