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Decoding Human Biology and Disease Using Single-Cell omics Technologies

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 926-949页

作者： Qiang Shi Xueyan Chen Zemin Zhang Biomedical Pioneering Innovation Center School of Life SciencesPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Changping Laboratory Beijing 102206China

Over the past decade,advances in Single-Cell omics(SCO)technologies have enabled the investigation of cellular heterogeneity at an unprecedented resolution and scale,opening a new avenue for understanding human biology and disease.In this review,we summarize the developments of sequencing-based SCO technologies and computational methods,and focus on considerable insights acquired from SCO sequencing studies to understand normal and diseased properties,with a particular emphasis on cancer research.We also discuss the technological improvements of SCO and its possible contribution to fundamental research of the human,as well as its great potential in clinical diagnoses and personalized therapies of human disease.

关键词： Single-Cell omics Computational method cellular heterogeneity Disease Cancer research

Application of Single-Cell omics in inflammatory bowel disease

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World Journal of Gastroenterology 2023年第28期29卷 4397-4404页

作者： Hengqi Betty Zheng Department of Pediatrics Seattle Children’s HospitalUniversity of WashingtonSeattleWA 98105United States

Over the past decade,the advent of single cell RNA-sequencing has revolutionized the approach in cellular transcriptomics research.The current technology offers an unbiased platform to understand how genotype correlates to phenotype.Single-Cell omics applications in gastrointestinal(GI)research namely inflammatory bowel disease(IBD)has become popular in the last few years with multiple publications as Single-Cell omics techniques can be applied directly to the target organ,the GI tract at the tissue level.Through examination of mucosal tissue and peripheral blood in IBD,the recent boom in single cell research has identified a myriad of key immune players from enterocytes to tissue resident memory T cells,and explored functional heterogeneity within cellular subsets previously unreported.As we begin to unravel the complex mucosal immune system in states of health and disease like IBD,the power of exploration through Single-Cell omics can change our approach to translational research.As novel techniques evolve through multiplexing Single-Cell omics and spatial transcriptomics come to the forefront,we can begin to fully comprehend the disease IBD and better design targets of treatment.In addition,hopefully these techniques can ultimately begin to identify biomarkers of therapeutic response and answer clinically relevant questions in how to tailor individual therapy to patients through personalized medicine.

关键词： Single-Cell omics Inflammatory bowel disease Crohn’s disease Ulcerative colitis single cell RNA-sequencing Precision medicine

omics Views of Mechanisms for cell Fate Determination in Early Mammalian Development

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 950-961页

作者： Lin-Fang Ju Heng-Ji Xu Yun-Gui Yang Ying Yang Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Institute of Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

During mammalian preimplantation development,a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination,ultimately forming a mature blastocyst.Along with compaction,the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice.Although the lineage segregation of the inner cell mass(ICM)and trophectoderm(TE)is the first symbol of cell differentiation,several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages,including the 2-and 4-cell stages.The underlying mechanisms of early cell fate determination have long been an important research topic.In this review,we summarize the molecular events that occur during early embryogenesis,as well as the current understanding of their regulatory roles in cell fate decisions.Moreover,as powerful tools for early embryogenesis research,Single-Cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate regulators.Here,we summarize their applications in the research of preimplantation embryos,and provide new insights and perspectives on cell fate regulation.

关键词： cell fate determination cellular heterogeneity cell polarity Single-Cell omics Mammalian preimplantation embryo

Network pharmacology approaches for research of Traditional Chinese Medicines

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Chinese Journal of Natural Medicines 2023年第5期21卷 323-332页

作者： LI Xiang LIU Ziqi LIAO Jie CHEN Qian LU Xiaoyan FAN Xiaohui School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical CollegeHangzhou 311399China Department of Chinese Medicine Science&Engineering College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Center in Zhejiang University State Key Laboratory of Component-based Chinese MedicineHangzhou 310058China Future Health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-target,multi-pathway”paradigm,show satisfactory clinical results in complex diseases.New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases.Network pharmacology(NP)provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases.The development and application of NP has promoted the safety,efficacy,and mechanism investigations of TCMs,which then reinforces the credibility and popularity of TCMs.The current organcentricity of medicine and the“one disease-one target-one drug”dogma obstruct the understanding of complex diseases and the development of effective drugs.Therefore,more attentions should be paid to shift from“phenotype and symptom”to“endotype and cause”in understanding and redefining current diseases.In the past two decades,with the advent of advanced and intelligent technologies(such as metabolomics,proteomics,transcriptomics,Single-Cell omics,and artificial intelligence),NP has been improved and deeply implemented,and presented its great value and potential as the next drug-discovery paradigm.NP is developed to cure causal mechanisms instead of treating symptoms.This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research,mechanism elucidation,target prediction,safety evaluation,drug repurposing,and drug design.

关键词： Network Pharmacology Single-Cell omics Artificial Intelligence Traditional Chinese Medicine Herbal Medicine Pharmacodynamics Material Basis Effective Mechanism Drug Repurposing

Recent advances in single-cell sequencing technologies

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Precision Clinical Medicine 2022年第1期5卷 13-22页

作者： Lu Wen Fuchou Tang Beijing Advanced Innovation Center for Genomics(ICG) Biomedical Pioneering Innovation Center(BIOPIC)School of Life SciencesPeking UniversityBeijing 100871China

Single-Cell omics sequencingwas first achieved for the transcriptome in 2009,whichwas followed by fast development of technologies for profiling the genome,DNA methylome,3D genome architecture,chromatin accessibility,histone modifications,etc.,in an individual cell.In this review we mainly focus on the recent progress in four topics in the Single-Cell omics field:single-cell epigenome sequencing,single-cell genome sequencing for lineage tracing,spatially resolved single-cell transcriptomics and third-generation sequencing platform-based Single-Cell omics sequencing.We also discuss the potential applications and future directions of these Single-Cell omics sequencing technologies for different biomedical systems,especially for the human stem cell field.

关键词： Single-Cell omics genome sequencing epigenome sequencing lineage tracing third-generation sequencing human stem cell