Publications by authors named "Hyeonkyeong Kim"

7 Publications

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Coordinate regulation of the senescent state by selective autophagy.

Dev Cell 2021 May 28;56(10):1512-1525.e7. Epub 2021 Apr 28.

School of Biological Sciences, Seoul National University, Seoul 08826, South Korea. Electronic address:

Cellular senescence is a complex stress response implicated in aging. Autophagy can suppress senescence but is counterintuitively necessary for full senescence. Although its anti-senescence role is well described, to what extent autophagy contributes to senescence establishment and the underlying mechanisms is poorly understood. Here, we show that selective autophagy of multiple regulatory components coordinates the homeostatic state of senescence. We combined a proteomic analysis of autophagy components with protein stability profiling, identifying autophagy substrate proteins involved in several senescence-related processes. Selective autophagy of KEAP1 promoted redox homeostasis during senescence. Furthermore, selective autophagy limited translational machinery components to ameliorate senescence-associated proteotoxic stress. Lastly, selective autophagy of TNIP1 enhanced senescence-associated inflammation. These selective autophagy networks appear to operate in vivo senescence during human osteoarthritis. Our data highlight a caretaker role of autophagy in the stress support network of senescence through regulated protein stability and unravel the intertwined relationship between two important age-related processes.
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http://dx.doi.org/10.1016/j.devcel.2021.04.008DOI Listing
May 2021

Enhanced third-harmonic generation by manipulating the twist angle of bilayer graphene.

Light Sci Appl 2021 Jan 21;10(1):19. Epub 2021 Jan 21.

Department of Energy Systems Research, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.

Twisted bilayer graphene (tBLG) has received substantial attention in various research fields due to its unconventional physical properties originating from Moiré superlattices. The electronic band structure in tBLG modified by interlayer interactions enables the emergence of low-energy van Hove singularities in the density of states, allowing the observation of intriguing features such as increased optical conductivity and photocurrent at visible or near-infrared wavelengths. Here, we show that the third-order optical nonlinearity can be considerably modified depending on the stacking angle in tBLG. The third-harmonic generation (THG) efficiency is found to significantly increase when the energy gap at the van Hove singularity matches the three-photon resonance of incident light. Further study on electrically tuneable optical nonlinearity reveals that the gate-controlled THG enhancement varies with the twist angle in tBLG, resulting in a THG enhanced up to 60 times compared to neutral monolayer graphene. Our results prove that the twist angle opens up a new way to control and increase the optical nonlinearity of tBLG, suggesting rotation-induced tuneable nonlinear optics in stacked two-dimensional material systems.
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http://dx.doi.org/10.1038/s41377-020-00459-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820413PMC
January 2021

Mixed-Dimensional In-Plane Heterostructures from 1D Mo Te and 2D MoTe Synthesized by Te-Flux-Controlled Chemical Vapor Deposition.

Small 2020 Nov 26;16(47):e2002849. Epub 2020 Oct 26.

Department of Chemistry, Ajou University, Suwon, 16499, Korea.

Mixed-dimensional van der Waals heterostructures are scientifically important and practically useful because of their interesting exotic properties resulting from their novel hybrid structures. This study reports the composition- and phase-selective fabrication of low-dimensional molybdenum/tellurium (Mo/Te) compounds and the direct synthesis of mixed-dimensional in-plane 1D-2D Mo Te -MoTe heterostructures. The composition and phase of the Mo/Te compounds are controlled by changing the Te atomic flux that is adjusted by the Te temperature. Metallic 1D Mo Te wires with an intrinsic 1D structure with a diameter of 3-8 nm and length of 100-300 nm are synthesized to form wire networks under low Te flux conditions, whereas the semiconducting few-layer 2H MoTe films preferentially oriented along the <0001> direction are obtained under high Te flux. Under medium Te flux, the mixed-dimensional in-plane 1D-2D Mo Te -MoTe heterostructures are synthesized in which the semiconducting few-layer 2H MoTe circular domains are edge-contacted by the metallic 1D Mo Te wire networks. Furthermore, the present Te-flux-controlled method reveals that the 1D Mo Te networks change to few-layer MoTe films as the Te flux increases. The in-plane 1D-2D Mo Te -MoTe heterostructures synthesized by this method can be considered as advanced edge-contacted 2D semiconductors for high-performance 2D electronics.
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http://dx.doi.org/10.1002/smll.202002849DOI Listing
November 2020

A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression.

Nat Commun 2020 10 6;11(1):5023. Epub 2020 Oct 6.

Center for RNA Research, Institute for Basic Science, 08826, Seoul, South Korea.

Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.
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http://dx.doi.org/10.1038/s41467-020-18817-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538956PMC
October 2020

Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation.

Nat Commun 2019 10 25;10(1):4898. Epub 2019 Oct 25.

Center for RNA Research, Institute for Basic Science, 08826, Seoul, South Korea.

Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
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http://dx.doi.org/10.1038/s41467-019-12910-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814715PMC
October 2019

Generation of an osteoblast-based artificial niche that supports in vitro B lymphopoiesis.

Exp Mol Med 2017 11 24;49(11):e400. Epub 2017 Nov 24.

Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.

B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells. Thus, development of a stable osteoblast cell line that can function as a biomimetic or artificial OBN is necessary. In this study, we developed a stable osteoblastic cell line, designated OBN4, which functions as an osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We demonstrated that the production of a B220 cell population from Lineage (Lin) Sca-1 c-Kit hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7-fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in coculture experiments. Consistently, OBN4 cells exhibited the highest production of B220 IgM cell populations (6.7±0.6-13.6±0.6%) in an IL-7- and stromal cell-derived factor 1-dependent manner, with higher production than primary osteoblasts (3.7±0.5-6.4±0.6%) and OP9 cells (1.8±0.6-3.9±0.5%). In addition, the production of B220 IgM IgD cell populations was significantly enhanced by OBN4 cells (15.4±1.1-18.9±3.2%) relative to production by primary osteoblasts (9.5±0.6-14.6±1.6%) and OP9 cells (9.1±0.5-10.3±1.8%). We conclude that OBN4 cells support in vitro B lymphopoiesis of Lin Sca-1 c-Kit HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.
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http://dx.doi.org/10.1038/emm.2017.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704192PMC
November 2017

Epigenetic Regulation of Chondrocyte Catabolism and Anabolism in Osteoarthritis.

Mol Cells 2015 Aug 5;38(8):677-84. Epub 2015 Aug 5.

Department of Biological Sciences, Seoul National University, Seoul 151-747, Korea.

Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OA-associated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.
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http://dx.doi.org/10.14348/molcells.2015.0200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546939PMC
August 2015
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