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  • MinireviewOctober 31, 2022

    2 1502 430

    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

    1 661 189

    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.

  • Journal ClubOctober 31, 2022

    0 575 135

    Fatty Exosomes Aggravate Metabolic Disorders

    Young Hyun Jung and Ho Jae Han

    Mol. Cells 2022; 45(10): 692-694
  • Research ArticleOctober 31, 2022

    0 840 223

    Abstract : Homeostatic regulation of meristematic stem cells accomplished by maintaining a balance between stem cell self-renewal and differentiation is critical for proper plant growth and development. The quiescent center (QC) regulates root apical meristem homeostasis by maintaining stem cell fate during plant root development. Cell cycle checkpoints, such as anaphase promoting complex/cyclosome/CELL CYCLE SWITCH 52 A2 (APC/CCCS52A2), strictly control the low proliferation rate of QC cells. Although APC/CCCS52A2 plays a critical role in maintaining QC cell division, the molecular mechanism that regulates its activity remains largely unknown. Here, we identified SCFF-BOX STRESS INDUCED 1 (FBS1), a ubiquitin E3 ligase, as a key regulator of QC cell division through the direct proteolysis of CCS52A2. FBS1 activity is positively associated with QC cell division and CCS52A2 proteolysis. FBS1 overexpression or ccs52a2-1 knockout consistently resulted in abnormal root development, characterized by root growth inhibition and low mitotic activity in the meristematic zone. Loss-of-function mutation of FBS1, on the other hand, resulted in low QC cell division, extremely low WOX5 expression, and rapid root growth. The 26S proteasome-mediated degradation of CCS52A2 was facilitated by its direct interaction with F-box stress induced 1 (FBS1). The FBS1 genetically interacted with APC/CCCS52A2-ERF115-PSKR1 signaling module for QC division. Thus, our findings establish SCFFBS1-mediated CCS52A2 proteolysis as the molecular mechanism for controlling QC cell division in plants.

  • Research ArticleOctober 31, 2022

    0 1458 194

    Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity

    Sang-Min Kang , Ji-Young Park , Hee-Jeong Han , Byeong-Min Song , Dongseob Tark , Byeong-Sun Choi , and Soon B. Hwang

    Mol. Cells 2022; 45(10): 702-717

    Abstract : Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulats beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediats protein interplay between NS5A and IKKε, thereby contributing to NS5A-mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

  • Research ArticleOctober 31, 2022

    1 981 296

    SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression

    Hyungmin Kim , Jeehan Lee , Soon-Young Jung , Hye Hyeon Yun , Jeong-Heon Ko , and Jeong-Hwa Lee

    Mol. Cells 2022; 45(10): 718-728

    Abstract : Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

  • Research ArticleOctober 31, 2022

    2 704 255

    Establishment and Characterization of Carboplatin-Resistant Retinoblastoma Cell Lines

    Chang Sik Cho , Dong Hyun Jo , Jin Hyoung Kim , and Jeong Hun Kim

    Mol. Cells 2022; 45(10): 729-737

    Abstract : Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed in vivo intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G0/G1 phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.

  • Research ArticleOctober 31, 2022

    6 1482 450

    The Peripheral Immune Landscape in a Patient with Myocarditis after the Administration of BNT162b2 mRNA Vaccine

    Bo Kyung Yoon , Tae Gyu Oh , Seonghyeon Bu , Kyung Jin Seo , Se Hwan Kwon , Ji Yoon Lee , Yeumin Kim , Jae-woo Kim , Hyo-Suk Ahn , and Sungsoon Fang

    Mol. Cells 2022; 45(10): 738-748

    Abstract : The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed a serious threat to global public health. A novel vaccine made from messenger RNA (mRNA) has been developed and approved for use at an unprecedented pace. However, an increased risk of myocarditis has been reported after BNT162b2 mRNA vaccination due to unknown causes. In this study, we used single-cell RNA sequencing and single-cell T cell receptor sequencing analyses of peripheral blood mononuclear cells (PBMCs) to describe, for the first time, changes in the peripheral immune landscape of a patient who underwent myocarditis after BNT162b2 vaccination. The greatest changes were observed in the transcriptomic profile of monocytes in terms of the number of differentially expressed genes. When compared to the transcriptome of PBMCs from vaccinated individuals without complications, increased expression levels of IL7R were detected in multiple cell clusters. Overall, results from this study can help advance research into the pathogenesis of BNT162b2-induced myocarditis.

  • Research ArticleOctober 31, 2022

    2 836 320

    PARK2 Induces Osteoclastogenesis through Activation of the NF-κB Pathway

    Seo Jin Hong , Suhan Jung , Ji Sun Jang , Shenzheng Mo , Jun-Oh Kwon , Min Kyung Kim , and Hong-Hee Kim *

    Mol. Cells 2022; 45(10): 749-760

    Abstract : Osteoclast generation from monocyte/macrophage lineage precursor cells needs to be tightly regulated to maintain bone homeostasis and is frequently over-activated in inflammatory conditions. PARK2, a protein associated with Parkinson’s disease, plays an important role in mitophagy via its ubiquitin ligase function. In this study, we investigated whether PARK2 is involved in osteoclastogenesis. PARK2 expression was found to be increased during the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. PARK2 gene silencing with siRNA significantly reduced osteoclastogenesis induced by RANKL, LPS (lipopolysaccharide), TNFα (tumor necrosis factor α), and IL-1β (interleukin-1β). On the other hand, overexpression of PARK2 promoted osteoclastogenesis. This regulation of osteoclastogenesis by PARK2 was mediated by IKK (inhibitory κB kinase) and NF-κB activation while MAPK (mitogen-activated protein kinases) activation was not involved. Additionally, administration of PARK2 siRNA significantly reduced osteoclastogenesis and bone loss in an in vivo model of inflammatory bone erosion. Taken together, this study establishes a novel role for PARK2 as a positive regulator in osteoclast differentiation and inflammatory bone destruction.

  • CorrigendumOctober 31, 2022

    0 310 108

    Corrigendum to: Downregulation of SETD5 Suppresses the Tumorigenicity of Hepatocellular Carcinoma Cells

    Mijin Park, Byul Moon, Jong-Hwan Kim, Seung-Jin Park, Seon-Kyu Kim, Kihyun Park, Jaehoon Kim, Seon-Young Kim, Jeong-Hoon Kim, and Jung-Ae Kim

    Mol. Cells 2022; 45(10): 761-761
Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.


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