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Article ; Online: Phytohormonal regulation determines the organization pattern of shoot aerenchyma in greater duckweed (Spirodela polyrhiza).

Kim, Min / Hyeon, Do Young / Kim, Kyungyoon / Hwang, Daehee / Lee, Yuree

2024

Abstract: Airspace or aerenchyma is crucial for plant development and acclimation to stresses such as hypoxia, drought, and nutritional deficiency. Although ethylene-mediated signaling cascades are known to regulate aerenchyma formation in stems and roots under ... ...

Abstract	Airspace or aerenchyma is crucial for plant development and acclimation to stresses such as hypoxia, drought, and nutritional deficiency. Although ethylene-mediated signaling cascades are known to regulate aerenchyma formation in stems and roots under hypoxic conditions, the precise mechanisms remain unclear. Moreover, the cellular dynamics underlying airspace formation in shoots are poorly understood. We investigated the stage-dependent structural dynamics of shoot aerenchyma in greater duckweed (Spirodela polyrhiza), a fast-growing aquatic herb with well-developed aerenchyma in its floating fronds. Using X-ray micro-computed tomography and histological analysis, we showed that the spatial framework of aerenchyma is established before frond volume increases, driven by cell division and expansion. The substomatal cavity connecting aerenchyma to stomata formed via programmed cell death (PCD) and was closely associated with guard cell development. Additionally, transcriptome analysis and pharmacological studies revealed that the organization of aerenchyma in common duckweed is determined by the interplay between PCD and proliferation. This balance is governed by spatiotemporal regulation of phytohormone signaling involving ethylene, abscisic acid, and salicylic acid. Overall, our study reveals the structural dynamics and phytohormonal regulation underlying aerenchyma development in duckweed, improving our understanding of how plants establish distinct architectural arrangements. These insights hold the potential for wide-ranging application, not only in comprehending aerenchyma formation across various plant species but also in understanding how airspaces are formed within the leaves of terrestrial plants.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	208914-2
ISSN	1532-2548 ; 0032-0889
ISSN (online)	1532-2548
ISSN	0032-0889
DOI	10.1093/plphys/kiae173
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Article ; Online: Single-cell multiomics: technologies and data analysis methods.

Lee, Jeongwoo / Hyeon, Do Young / Hwang, Daehee

Experimental & molecular medicine

2020 Volume 52, Issue 9, Page(s) 1428–1442

Abstract: Advances in single-cell isolation and barcoding technologies offer unprecedented opportunities to profile DNA, mRNA, and proteins at a single-cell resolution. Recently, bulk multiomics analyses, such as multidimensional genomic and proteogenomic analyses, ...

Abstract	Advances in single-cell isolation and barcoding technologies offer unprecedented opportunities to profile DNA, mRNA, and proteins at a single-cell resolution. Recently, bulk multiomics analyses, such as multidimensional genomic and proteogenomic analyses, have proven beneficial for obtaining a comprehensive understanding of cellular events. This benefit has facilitated the development of single-cell multiomics analysis, which enables cell type-specific gene regulation to be examined. The cardinal features of single-cell multiomics analysis include (1) technologies for single-cell isolation, barcoding, and sequencing to measure multiple types of molecules from individual cells and (2) the integrative analysis of molecules to characterize cell types and their functions regarding pathophysiological processes based on molecular signatures. Here, we summarize the technologies for single-cell multiomics analyses (mRNA-genome, mRNA-DNA methylation, mRNA-chromatin accessibility, and mRNA-protein) as well as the methods for the integrative analysis of single-cell multiomics data.
MeSH term(s)	Animals ; Biotechnology ; Computational Biology/methods ; Computational Biology/standards ; Epigenomics/methods ; Gene Expression Profiling/methods ; Genomics/methods ; Genomics/standards ; Humans ; Organ Specificity/genetics ; Proteomics/methods ; Single-Cell Analysis/methods ; Single-Cell Analysis/standards ; Transcriptome
Language	English
Publishing date	2020-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-020-0420-2
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Article ; Online: E3 ligase BRUTUS Is a Negative Regulator for the Cellular Energy Level and the Expression of Energy Metabolism-Related Genes Encoded by Two Organellar Genomes in Leaf Tissues.

Choi, Bongsoo / Hyeon, Do Young / Lee, Juhun / Long, Terri A / Hwang, Daehee / Hwang, Inhwan

Molecules and cells

2022 Volume 45, Issue 5, Page(s) 294–305

Abstract: E3 ligase BRUTUS (BTS), a putative iron sensor, is expressed in both root and shoot tissues in seedlings ... ...

Abstract	E3 ligase BRUTUS (BTS), a putative iron sensor, is expressed in both root and shoot tissues in seedlings of
MeSH term(s)	Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Arabidopsis/metabolism ; Arabidopsis Proteins/metabolism ; Energy Metabolism/genetics ; Gene Expression Regulation, Plant ; Plant Leaves/genetics ; Plant Leaves/metabolism ; Plant Roots/genetics ; Plant Roots/metabolism ; Plant Shoots ; Starch/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Arabidopsis Proteins ; Adenosine Diphosphate (61D2G4IYVH) ; Adenosine Triphosphate (8L70Q75FXE) ; Starch (9005-25-8) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2022.2029
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Article ; Online: Morc2a variants cause hydroxyl radical-mediated neuropathy and are rescued by restoring GHKL ATPase.

Chung, Hye Yoon / Lee, Geon Seong / Nam, Soo Hyun / Lee, Jeong Hyeon / Han, Jeong Pil / Song, Sumin / Kim, Gap-Don / Jung, Choonkyun / Hyeon, Do Young / Hwang, Daehee / Choi, Byung-Ok / Yeom, Su Cheong

Brain : a journal of neurology

2024

Abstract: Mutations in the Microrchidia CW-Type Zinc Finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we ... ...

Abstract	Mutations in the Microrchidia CW-Type Zinc Finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high central nervous system transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss of functional characteristics due to protein synthesis defects in Morc2a p.S87L was also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy.
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awae017
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Article ; Online: Integrative analysis of transcriptomic data for identification of T-cell activation-related mRNA signatures indicative of preterm birth.

Yoo, Jae Young / Hyeon, Do Young / Shin, Yourae / Kim, Soo Min / You, Young-Ah / Kim, Daye / Hwang, Daehee / Kim, Young Ju

Scientific reports

2021 Volume 11, Issue 1, Page(s) 2392

Abstract: Preterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. ... ...

Abstract	Preterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. However, due to the redundant nature of the clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of PTB. To identify molecular signatures predictive of PTB with high accuracy, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) as well as cellular pathways represented by the DEGs between PTB and FTB. By integrating the gene expression profiles of different ethnic groups from previous studies, we identified the core T-cell activation pathway associated with PTB, which was shared among all previous datasets, and selected three representative DEGs (CYLD, TFRC, and RIPK2) from the core pathway as mRNA signatures predictive of PTB. We confirmed the dysregulation of the candidate predictors and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 are potentially reliable predictors for PTB.
Language	English
Publishing date	2021-01-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-81834-z
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Article ; Online: Evolution of the multi-tRNA synthetase complex and its role in cancer.

Hyeon, Do Young / Kim, Jong Hyun / Ahn, Tae Jin / Cho, Yeshin / Hwang, Daehee / Kim, Sunghoon

The Journal of biological chemistry

2019 Volume 294, Issue 14, Page(s) 5340–5351

Abstract: Aminoacyl-tRNA synthetases (ARSs) are enzymes that ligate their cognate amino acids to tRNAs for protein synthesis. However, recent studies have shown that their functions are expanded beyond protein synthesis through the interactions with diverse ... ...

Abstract	Aminoacyl-tRNA synthetases (ARSs) are enzymes that ligate their cognate amino acids to tRNAs for protein synthesis. However, recent studies have shown that their functions are expanded beyond protein synthesis through the interactions with diverse cellular factors. In this review, we discuss how ARSs have evolved to expand and control their functions by forming protein assemblies. We particularly focus on a macromolecular ARS complex in eukaryotes, named multi-tRNA synthetase complex (MSC), which is proposed to provide a channel through which tRNAs reach bound ARSs to receive their cognate amino acid and transit further to the translation machinery. Approximately half of the ARSs assemble into the MSC through
MeSH term(s)	Amino Acyl-tRNA Synthetases/genetics ; Amino Acyl-tRNA Synthetases/metabolism ; Animals ; DNA Repair ; Evolution, Molecular ; Humans ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/enzymology ; Neoplasms/genetics ; Neoplasms/pathology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Multienzyme Complexes ; Neoplasm Proteins ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-)
Language	English
Publishing date	2019-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.REV118.002958
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Article: Ethylene responsive factor34 mediates stress‐induced leaf senescence by regulating salt stress‐responsive genes

Park, Sung‐Jin / Park, Sanghoon / Kim, Yongmin / Hyeon, Do Young / Park, Hyunsoo / Jeong, Junyong / Jeong, Ukcheol / Yoon, Yeong Seon / You, Daesang / Kwak, Junmin / Timilsina, Rupak / Hwang, Daehee / Kim, Jeongsik / Woo, Hye Ryun

Plant, cell and environment. 2022 June, v. 45, no. 6

2022

Abstract: Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well‐known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt ... ...

Abstract	Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well‐known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt stress signalling with leaf senescence programmes remain elusive. In this study, we characterised the role of ETHYLENE RESPONSIVE FACTOR34 (ERF34), an Arabidopsis APETALA2 (AP2)/ERF family transcription factor, in leaf senescence. ERF34 was differentially expressed under various leaf senescence‐inducing conditions, and negatively regulated leaf senescence induced by age, dark, and salt stress. ERF34 also promoted salt stress tolerance at different stages of the plant life cycle such as seed germination and vegetative growth. Transcriptome analysis revealed that the overexpression of ERF34 increased the transcript levels of salt stress‐responsive genes including COLD‐REGULATED15A (COR15A), EARLY RESPONSIVE TO DEHYDRATION10 (ERD10), and RESPONSIVE TO DESICCATION29A (RD29A). Moreover, ERF34 directly bound to ERD10 and RD29A promoters and activated their expression. Our findings indicate that ERF34 plays a key role in the convergence of the salt stress response with the leaf senescence programmes, and is a potential candidate for crop improvement, particularly by enhancing salt stress tolerance.
Keywords	Arabidopsis ; environment ; ethylene ; leaves ; salt stress ; seed germination ; stress response ; stress tolerance ; transcription factors ; transcriptomics ; vegetative growth
Language	English
Dates of publication	2022-06
Size	p. 1719-1733.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	391893-2
ISSN	1365-3040 ; 0140-7791
ISSN (online)	1365-3040
ISSN	0140-7791
DOI	10.1111/pce.14317
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141

Kim, Duk Ki / Jeong, Juhee / Lee, Dong Sun / Hyeon, Do Young / Park, Geon Woo / Jeon, Suwan / Lee, Kyung Bun / Jang, Jin-Young / Hwang, Daehee / Kim, Ho Min / Jung, Keehoon

Nature communications

2022 Volume 13, Issue 1, Page(s) 6292

Abstract: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141
MeSH term(s)	Female ; Humans ; Cancer-Associated Fibroblasts/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Placenta Growth Factor/genetics ; Placenta Growth Factor/metabolism ; Single-Chain Antibodies/metabolism ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Antineoplastic Agents/pharmacology ; Fibrosis ; Pancreatic Neoplasms
Chemical Substances	Vascular Endothelial Growth Factor A ; Placenta Growth Factor (144589-93-5) ; Single-Chain Antibodies ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; Antineoplastic Agents
Language	English
Publishing date	2022-10-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33991-6
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Article ; Online: Ethylene responsive factor34 mediates stress-induced leaf senescence by regulating salt stress-responsive genes.

Park, Sung-Jin / Park, Sanghoon / Kim, Yongmin / Hyeon, Do Young / Park, Hyunsoo / Jeong, Junyong / Jeong, Ukcheol / Yoon, Yeong Seon / You, Daesang / Kwak, Junmin / Timilsina, Rupak / Hwang, Daehee / Kim, Jeongsik / Woo, Hye Ryun

Plant, cell & environment

2022 Volume 45, Issue 6, Page(s) 1719–1733

Abstract: Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well-known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt ... ...

Abstract	Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well-known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt stress signalling with leaf senescence programmes remain elusive. In this study, we characterised the role of ETHYLENE RESPONSIVE FACTOR34 (ERF34), an Arabidopsis APETALA2 (AP2)/ERF family transcription factor, in leaf senescence. ERF34 was differentially expressed under various leaf senescence-inducing conditions, and negatively regulated leaf senescence induced by age, dark, and salt stress. ERF34 also promoted salt stress tolerance at different stages of the plant life cycle such as seed germination and vegetative growth. Transcriptome analysis revealed that the overexpression of ERF34 increased the transcript levels of salt stress-responsive genes including COLD-REGULATED15A (COR15A), EARLY RESPONSIVE TO DEHYDRATION10 (ERD10), and RESPONSIVE TO DESICCATION29A (RD29A). Moreover, ERF34 directly bound to ERD10 and RD29A promoters and activated their expression. Our findings indicate that ERF34 plays a key role in the convergence of the salt stress response with the leaf senescence programmes, and is a potential candidate for crop improvement, particularly by enhancing salt stress tolerance.
MeSH term(s)	Arabidopsis/metabolism ; Ethylenes/metabolism ; Gene Expression Regulation, Plant ; Plant Senescence ; Salt Stress ; Stress, Physiological/genetics
Chemical Substances	Ethylenes
Language	English
Publishing date	2022-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391893-2
ISSN	1365-3040 ; 0140-7791
ISSN (online)	1365-3040
ISSN	0140-7791
DOI	10.1111/pce.14317
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Article ; Online: BAP1 shapes the bone marrow niche for lymphopoiesis by fine-tuning epigenetic profiles in endosteal mesenchymal stromal cells.

Jeong, Jinguk / Jung, Inkyung / Kim, Ji-Hoon / Jeon, Shin / Hyeon, Do Young / Min, Hyungyu / Kang, Byeonggeun / Nah, Jinwoo / Hwang, Daehee / Um, Soo-Jong / Ko, Myunggon / Seong, Rho Hyun

Cell death and differentiation

2022 Volume 29, Issue 11, Page(s) 2151–2162

Abstract: Hematopoiesis occurs within a unique bone marrow (BM) microenvironment, which consists of various niche cells, cytokines, growth factors, and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and ... ...

Abstract	Hematopoiesis occurs within a unique bone marrow (BM) microenvironment, which consists of various niche cells, cytokines, growth factors, and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and differentiation of hematopoietic stem cells (HSCs). Here we report that BAP1 in BM mesenchymal stromal cells (MSCs) is critical for the maintenance of HSCs and B lymphopoiesis. Mice lacking BAP1 in MSCs show aberrant differentiation of hematopoietic stem and progenitor cells, impaired B lymphoid differentiation, and expansion of myeloid lineages. Mechanistically, BAP1 loss in distinct endosteal MSCs, expressing PRX1 but not LEPR, leads to aberrant expression of genes affiliated with BM niche functions. BAP1 deficiency leads to a reduced expression of pro-hematopoietic factors such as Scf caused by increased H2AK119-ub1 and H3K27-me3 levels on the promoter region of these genes. On the other hand, the expression of myelopoiesis stimulating factors including Csf3 was increased by enriched H3K4-me3 and H3K27-ac levels on their promoter, causing myeloid skewing. Notably, loss of BAP1 substantially blocks B lymphopoiesis and skews the differentiation of hematopoietic precursors toward myeloid lineages in vitro, which is reversed by G-CSF neutralization. Thus, our study uncovers a key role for BAP1 expressed in endosteal MSCs in controlling normal hematopoiesis in mice by modulating expression of various niche factors governing lymphopoiesis and myelopoiesis via histone modifications.
MeSH term(s)	Mice ; Animals ; Lymphopoiesis/genetics ; Bone Marrow/metabolism ; Mesenchymal Stem Cells/metabolism ; Hematopoietic Stem Cells/metabolism ; Hematopoiesis/genetics ; Bone Marrow Cells ; Cell Differentiation/genetics ; Granulocyte Colony-Stimulating Factor ; Epigenesis, Genetic ; Stem Cell Niche/genetics ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Granulocyte Colony-Stimulating Factor (143011-72-7) ; BAP1 protein, mouse ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2022-04-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-022-01006-y
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