• MinireviewDecember 31, 2022

    0 707 204

    Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

    Ji-Young Kim , Ji-Hye Jung , Seung-Joon Lee , Seon-Sook Han , and Seok-Ho Hong

    Mol. Cells 2022; 45(12): 869-876

    Abstract : Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

  • MinireviewDecember 31, 2022

    0 413 94

    Advances in Optical Tools to Study Taste Sensation

    Gha Yeon Park , Hyeyeong Hwang , and Myunghwan Choi

    Mol. Cells 2022; 45(12): 877-882

    Abstract : Taste sensation is the process of converting chemical identities in food into a neural code of the brain. Taste information is initially formed in the taste buds on the tongue, travels through the afferent gustatory nerves to the sensory ganglion neurons, and finally reaches the multiple taste centers of the brain. In the taste field, optical tools to observe cellular-level functions play a pivotal role in understanding how taste information is processed along a pathway. In this review, we introduce recent advances in the optical tools used to study the taste transduction pathways.

  • MinireviewNovember 30, 2022

    0 476 115

    Abstract : Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders. We will conclude with a potential mechanism of proline metabolism in neuronal function and mental health.

  • MinireviewNovember 30, 2022

    0 779 235

    Abstract : Caenorhabditis elegans has been used as a major model organism to identify genetic factors that regulate organismal aging and longevity. Insulin/insulin-like growth factor 1 (IGF- 1) signaling (IIS) regulates aging in many species, ranging from nematodes to humans. C. elegans is a nonpathogenic genetic nematode model, which has been extensively utilized to identify molecular and cellular components that function in organismal aging and longevity. Here, we review the recent progress in the role of IIS in aging and longevity, which involves direct regulation of protein and RNA homeostasis, stress resistance, metabolism and the activities of the endocrine system. We also discuss recently identified genetic factors that interact with canonical IIS components to regulate aging and health span in C. elegans. We expect this review to provide valuable insights into understanding animal aging, which could eventually help develop anti-aging drugs for humans.

  • MinireviewNovember 30, 2022

    0 579 189

    Abstract : The field of extracellular vesicles (EVs) has expanded tremendously over the last decade. The role of cell-to-cell communication in neighboring or distant cells has been increasingly ascribed to EVs generated by various cells. Initially, EVs were thought to a means of cellular debris or disposal system of unwanted cellular materials that provided an alternative to autolysis in lysosomes. Intercellular exchange of information has been considered to be achieved by well-known systems such as hormones, cytokines, and nervous networks. However, most research in this field has searched for and found evidence to support paracrine or endocrine roles of EV, which inevitably leads to a new concept that EVs are synthesized to achieve their paracrine or endocrine purposes. Here, we attempted to verify the endocrine role of EV production and their contents, such as RNAs and bioactive proteins, from the regulation of biogenesis, secretion, and action mechanisms while discussing the current technical limitations. It will also be important to discuss how blood EV concentrations are regulated as if EVs are humoral endocrine machinery.

  • MinireviewOctober 31, 2022

    0 1020 281

    The Single-Cell Revelation of Thermogenic Adipose Tissue

    Yue Qi and Xiaoyan Hannah Hui

    Mol. Cells 2022; 45(10): 673-684

    Abstract : The past two decades have witnessed an upsurge in the appreciation of adipose tissue (AT) as an immuno-metabolic hub harbouring heterogeneous cell populations that collectively fine-tune systemic metabolic homeostasis. Technological advancements, especially single-cell transcriptomics, have offered an unprecedented opportunity for dissecting the sophisticated cellular networks and compositional dynamics underpinning AT remodelling. The “re-discovery” of functional brown adipose tissue dissipating heat energy in human adults has aroused tremendous interest in exploiting the mechanisms underpinning the engagement of AT thermogenesis for combating human obesity. In this review, we aim to summarise and evaluate the use of single-cell transcriptomics that contribute to a better appreciation of the cellular plasticity and intercellular crosstalk in thermogenic AT.

  • MinireviewOctober 31, 2022

    0 481 129

    Abstract : Early-life environmental factors can have persistent effects on physiological functions by altering developmental procedures in various organisms. Recent experimental and epidemiological studies now further support the idea that developmental programming is also present in mammals, including humans, influencing long-term health. Although the mechanism of programming is still largely under investigation, the role of endocrine glucocorticoids in developmental programming is gaining interest. Studies found that perinatal glucocorticoids have a persistent effect on multiple functions of the body, including metabolic, behavioral, and immune functions, in adulthood. Several mechanisms have been proposed to play a role in long-term programming. In this review, recent findings on this topic are summarized and the potential biological rationale behind this phenomenon is discussed.

  • MinireviewSeptember 30, 2022

    2 2009 581

    Transcriptional Heterogeneity of Cellular Senescence in Cancer

    Muhammad Junaid , Aejin Lee , Jaehyung Kim , Tae Jun Park , and Su Bin Lim

    Mol. Cells 2022; 45(9): 610-619

    Abstract : Cellular senescence plays a paradoxical role in tumorigenesis through the expression of diverse senescence-associated (SA) secretory phenotypes (SASPs). The heterogeneity of SA gene expression in cancer cells not only promotes cancer stemness but also protects these cells from chemotherapy. Despite the potential correlation between cancer and SA biomarkers, many transcriptional changes across distinct cell populations remain largely unknown. During the past decade, single-cell RNA sequencing (scRNA-seq) technologies have emerged as powerful experimental and analytical tools to dissect such diverse senescence-derived transcriptional changes. Here, we review the recent sequencing efforts that successfully characterized scRNA-seq data obtained from diverse cancer cells and elucidated the role of senescent cells in tumor malignancy. We further highlight the functional implications of SA genes expressed specifically in cancer and stromal cell populations in the tumor microenvironment. Translational research leveraging scRNA-seq profiling of SA genes will facilitate the identification of novel expression patterns underlying cancer susceptibility, providing new therapeutic opportunities in the era of precision medicine.

  • MinireviewSeptember 30, 2022

    3 1705 579

    The Role of Extracellular Vesicles in Senescence

    Chaehwan Oh , Dahyeon Koh , Hyeong Bin Jeon , and Kyoung Mi Kim

    Mol. Cells 2022; 45(9): 603-609

    Abstract : Cells can communicate in a variety of ways, such as by contacting each other or by secreting certain factors. Recently, extracellular vesicles (EVs) have been proposed to be mediators of cell communication. EVs are small vesicles with a lipid bilayer membrane that are secreted by cells and contain DNA, RNAs, lipids, and proteins. These EVs are secreted from various cell types and can migrate and be internalized by recipient cells that are the same or different than those that secrete them. EVs harboring various components are involved in regulating gene expression in recipient cells. These EVs may also play important roles in the senescence of cells and the accumulation of senescent cells in the body. Studies on the function of EVs in senescent cells and the mechanisms through which nonsenescent and senescent cells communicate through EVs are being actively conducted. Here, we summarize studies suggesting that EVs secreted from senescent cells can promote the senescence of other cells and that EVs secreted from nonsenescent cells can rejuvenate senescent cells. In addition, we discuss the functional components (proteins, RNAs, and other molecules) enclosed in EVs that enter recipient cells.

  • MinireviewAugust 31, 2022

    3 1134 329

    Abstract : Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.

  • MinireviewAugust 31, 2022

    0 823 200

    Z-DNA?Containing Long Terminal Repeats of Human Endogenous Retrovirus Families Provide Alternative Promoters for Human Functional Genes

    Du Hyeong Lee , Woo Hyeon Bae , Hongseok Ha , Eun Gyung Park , Yun Ju Lee , Woo Ryung Kim , and Heui-Soo Kim

    Mol. Cells 2022; 45(8): 522-530

    Abstract : Transposable elements (TEs) account for approximately 45% of the human genome. TEs have proliferated randomly and integrated into functional genes during hominoid radiation. They appear as right-handed B-DNA double helices and slightly elongated left-handed Z-DNAs. Human endogenous retrovirus (HERV) families are widely distributed in human chromosomes at a ratio of 8%. They contain a 5′-long terminal repeat (LTR)-gag-pol-env-3′-LTR structure. LTRs contain the U3 enhancer and promoter region, transcribed R region, and U5 region. LTRs can influence host gene expression by acting as regulatory elements. In this review, we describe the alternative promoters derived from LTR elements that overlap Z-DNA by comparing Z-hunt and DeepZ data for human functional genes. We also present evidence showing the regulatory activity of LTR elements containing Z-DNA in GSDML. Taken together, the regulatory activity of LTR elements with Z-DNA allows us to understand gene function in relation to various human diseases.

  • MinireviewJuly 31, 2022

    8 1663 430

    m6A in the Signal Transduction Network

    Ki-Hong Jang , Chloe R. Heras , and Gina Lee

    Mol. Cells 2022; 45(7): 435-443

    Abstract : In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. Epigenetic modification of the transcribed RNA can be another layer of gene expression regulation. N6-adenosine methylation (m6A) is one of the most common modifications on mRNA. It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. m6A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m6A processing. Conversely, m6A can modulate the activity of signal transduction networks via m6A modification of signaling pathway genes or by acting as a ligand for receptors. In this review, we discuss the current understanding of the crosstalk between m6A and signaling pathways and its implication for biological systems.

Mol. Cells
Feb 28, 2023 Vol.46 No.2, pp. 69~129
The bulk tissue is a heterogeneous mixture of various cell types, which is depicted as a skein of intertwined threads with diverse colors each of which represents a unique cell type. Single-cell omics analysis untangles efficiently the skein according to the color by providing information of molecules at individual cells and interpretation of such information based on different cell types. The molecules that can be profiled at the individual cell by single-cell omics analysis includes DNA (bottom middle), RNA (bottom right), and protein (bottom left). This special issue reviews single-cell technologies and computational methods that have been developed for the single-cell omics analysis and how they have been applied to improve our understanding of the underlying mechanisms of biological and pathological phenomena at the single-cell level.

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