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  • Journal Club 2021-11-30

    0 113 29

    Migrating Cells Dispose of Damaged Mitochondria into the Surrounding Environment

    Mitochondria quality control coupled with cell migration in mammalian in vivo model

    Choong-Sil Lee and Jaewhan Song

    Mol. Cells 2021; 44(11): 781-783 https://doi.org/10.14348/molcells.2021.5007
  • Research Article 2021-11-30

    0 190 57

    TJP1 Contributes to Tumor Progression through Supporting Cell-Cell Aggregation and Communicating with Tumor Microenvironment in Leiomyosarcoma

    Eun-Young Lee , Minjeong Kim , Beom K. Choi , Dae Hong Kim , Inho Choi , and Hye Jin You

    Mol. Cells 2021; 44(11): 784-794 https://doi.org/10.14348/molcells.2021.0130
    Abstract

    Abstract : Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.

  • Research Article 2021-11-30

    0 93 33

    Neural-Cadherin Influences the Homing of Terminally Differentiated Memory CD8 T Cells to the Lymph Nodes and Bone Marrow

    Kyong Hoon Kim , Aryeong Choi , Sang Hoon Kim , Heonju Song , Seohoon Jin , Kyungim Kim , Jaebong Jang , Hanbyeul Choi , and Yong Woo Jung

    Mol. Cells 2021; 44(11): 795-804 https://doi.org/10.14348/molcells.2021.0137
    Abstract

    Abstract : Memory T (TM) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how TM cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, TM cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin+ cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of TM cells. The numbers of CD127hiCD62Lhi TM cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127loKLRG1hi TM cells were adoptively transferred into anti–N-cadherin–treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, without functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127hiCD62Lhi TM cells and homing of CD127loKLRG1hi TM cells to lymphoid organs.

  • Research Article 2021-11-30

    0 257 91

    CHD4 Conceals Aberrant CTCF-Binding Sites at TAD Interiors by Regulating Chromatin Accessibility in Mouse Embryonic Stem Cells

    Sungwook Han , Hosuk Lee , Andrew J. Lee , Seung-Kyoon Kim , Inkyung Jung , Gou Young Koh , Tae-Kyung Kim , and Daeyoup Lee

    Mol. Cells 2021; 44(11): 805-829 https://doi.org/10.14348/molcells.2021.0224
    Abstract

    Abstract : CCCTC-binding factor (CTCF) critically contributes to 3D chromatin organization by determining topologically associated domain (TAD) borders. Although CTCF primarily binds at TAD borders, there also exist putative CTCF-binding sites within TADs, which are spread throughout the genome by retrotransposition. However, the detailed mechanism responsible for masking the putative CTCF-binding sites remains largely elusive. Here, we show that the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding 4 (CHD4), regulates chromatin accessibility to conceal aberrant CTCF-binding sites embedded in H3K9me3-enriched heterochromatic B2 short interspersed nuclear elements (SINEs) in mouse embryonic stem cells (mESCs). Upon CHD4 depletion, these aberrant CTCF-binding sites become accessible and aberrant CTCF recruitment occurs within TADs, resulting in disorganization of local TADs. RNA-binding intrinsically disordered domains (IDRs) of CHD4 are required to prevent this aberrant CTCF binding, and CHD4 is critical for the repression of B2 SINE transcripts. These results collectively reveal that a CHD4-mediated mechanism ensures appropriate CTCF binding and associated TAD organization in mESCs.

  • Research Article 2021-11-30

    0 241 72

    The Danger-Associated Peptide PEP1 Directs Cellular Reprogramming in the Arabidopsis Root Vascular System

    Souvik Dhar , Hyoujin Kim , Cécile Segonzac , and Ji-Young Lee

    Mol. Cells 2021; 44(11): 830-842 https://doi.org/10.14348/molcells.2021.0203
    Abstract

    Abstract : When perceiving microbe-associated molecular patterns (MAMPs) or plant-derived damage-associated molecular patterns (DAMPs), plants alter their root growth and development by displaying a reduction in the root length and the formation of root hairs and lateral roots. The exogenous application of a MAMP peptide, flg22, was shown to affect root growth by suppressing meristem activity. In addition to MAMPs, the DAMP peptide PEP1 suppresses root growth while also promoting root hair formation. However, the question of whether and how these elicitor peptides affect the development of the vascular system in the root has not been explored. The cellular receptors of PEP1, PEPR1 and PEPR2 are highly expressed in the root vascular system, while the receptors of flg22 (FLS2) and elf18 (EFR) are not. Consistent with the expression patterns of PEP1 receptors, we found that exogenously applied PEP1 has a strong impact on the division of stele cells, leading to a reduction of these cells. We also observed the alteration in the number and organization of cells that differentiate into xylem vessels. These PEP1-mediated developmental changes appear to be linked to the blockage of symplastic connections triggered by PEP1. PEP1 dramatically disrupts the symplastic movement of free green fluorescence protein (GFP) from phloem sieve elements to neighboring cells in the root meristem, leading to the deposition of a high level of callose between cells. Taken together, our first survey of PEP1-mediated vascular tissue development provides new insights into the PEP1 function as a regulator of cellular reprogramming in the Arabidopsis root vascular system.

  • Research Article 2021-11-30

    0 131 32

    Q-omics: Smart Software for Assisting Oncology and Cancer Research

    Jieun Lee , Youngju Kim , Seonghee Jin , Heeseung Yoo , Sumin Jeong , Euna Jeong , and Sukjoon Yoon

    Mol. Cells 2021; 44(11): 843-850 https://doi.org/10.14348/molcells.2021.0169
    Abstract

    Abstract : The rapid increase in collateral omics and phenotypic data has enabled data-driven studies for the fast discovery of cancer targets and biomarkers. Thus, it is necessary to develop convenient tools for general oncologists and cancer scientists to carry out customized data mining without computational expertise. For this purpose, we developed innovative software that enables user-driven analyses assisted by knowledge-based smart systems. Publicly available data on mutations, gene expression, patient survival, immune score, drug screening and RNAi screening were integrated from the TCGA, GDSC, CCLE, NCI, and DepMap databases. The optimal selection of samples and other filtering options were guided by the smart function of the software for data mining and visualization on Kaplan-Meier plots, box plots and scatter plots of publication quality. We implemented unique algorithms for both data mining and visualization, thus simplifying and accelerating user-driven discovery activities on large multiomics datasets. The present Q-omics software program (v0.95) is available at http://qomics.sookmyung.ac.kr.

  • Research Article 2021-11-30

    0 307 36

    Characterizing Organelles in Live Stem Cells Using Label-Free Optical Diffraction Tomography

    Youngkyu Kim , Tae-Keun Kim , Yeonhee Shin , Eunyoung Tak , Gi-Won Song , Yeon-Mok Oh , Jun Ki Kim , and Chan-Gi Pack

    Mol. Cells 2021; 44(11): 851-860 https://doi.org/10.14348/molcells.2021.0190
    Abstract

    Abstract : Label-free optical diffraction tomography (ODT), an imaging technology that does not require fluorescent labeling or other pre-processing, can overcome the limitations of conventional cell imaging technologies, such as fluorescence and electron microscopy. In this study, we used ODT to characterize the cellular organelles of three different stem cells—namely, human liver derived stem cell, human umbilical cord matrix derived mesenchymal stem cell, and human induced pluripotent stem cell—based on their refractive index and volume of organelles. The physical property of each stem cell was compared with that of fibroblast. Based on our findings, the characteristic physical properties of specific stem cells can be quantitatively distinguished based on their refractive index and volume of cellular organelles. Altogether, the method employed herein could aid in the distinction of living stem cells from normal cells without the use of fluorescence or specific biomarkers.

Mol. Cells
Nov 30, 2021 Vol.44 No.11, pp. 781~860
COVER PICTURE
3D quantitative images of the vesicular structure and the nucleolus using label free optical diffraction tomography (Kim et al., pp. 851-860).

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