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Article ; Online: The discovery of gut microbial metabolites as modulators of host susceptibility to acetaminophen-induced hepatotoxicity.

Lee, Hyunwoo / Yang, Xiaotong / Jin, Pei-Ru / Won, Kyoung-Jae / Kim, Chang H / Jeong, Hyunyoung

Drug metabolism and disposition: the biological fate of chemicals

2024

Abstract: The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is the ... ...

Abstract	The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is the organ massively exposed to gut microbial metabolites, and it serves as the nexus, maintaining healthy interactions between the gut microbiota and host. At the same time, the liver is the primary target of harmful gut microbial metabolites. This review provides an up-to-date list of gut microbial metabolites identified to increase or decrease host susceptibility to APAP-induced liver injury. Signaling pathways and molecular factors involved in the progression of APAP-induced hepatotoxicity are well-established, and we propose that the mouse model of APAP-induced hepatotoxicity serves as an excellent system for uncovering gut microbial metabolites of previously unknown function. Moreover, we envision that gut microbial metabolites identified to alter APAP-induced hepatotoxicity likely have broader implications in other liver diseases.
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	186795-7
ISSN	1521-009X ; 0090-9556
ISSN (online)	1521-009X
ISSN	0090-9556
DOI	10.1124/dmd.123.001541
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Zs.A 1014: Show issues

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Article ; Online: Mapping Cellular Coordinates through Advances in Spatial Transcriptomics Technology.

Teves, Joji Marie / Won, Kyoung Jae

Molecules and cells

2020 Volume 43, Issue 7, Page(s) 591–599

Abstract: Complex cell-to-cell communication underlies the basic processes essential for homeostasis in the given tissue architecture. Obtaining quantitative gene-expression of cells in their native context has significantly advanced through single-cell RNA ... ...

Abstract	Complex cell-to-cell communication underlies the basic processes essential for homeostasis in the given tissue architecture. Obtaining quantitative gene-expression of cells in their native context has significantly advanced through single-cell RNA sequencing technologies along with mechanical and enzymatic tissue manipulation. This approach, however, is largely reliant on the physical dissociation of individual cells from the tissue, thus, resulting in a library with unaccounted positional information. To overcome this, positional information can be obtained by integrating imaging and positional barcoding. Collectively, spatial transcriptomics strategies provide tissue architecture-dependent as well as position-dependent cellular functions. This review discusses the current technologies for spatial transcriptomics ranging from the methods combining mechanical dissociation and single-cell RNA sequencing to computational spatial re-mapping.
MeSH term(s)	Cell Communication/physiology ; Computational Biology/methods ; Gene Expression Profiling/methods ; High-Throughput Nucleotide Sequencing/methods ; In Situ Hybridization, Fluorescence/methods ; Single-Cell Analysis/methods ; Spatial Analysis ; Transcriptome
Language	English
Publishing date	2020-05-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2020.0020
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Zs.A 4713: Show issues

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Article: Single Cell RNA-Sequencing for the Study of Atherosclerosis.

Hajkarim, Morteza Chalabi / Won, Kyoung Jae

Journal of lipid and atherosclerosis

2019 Volume 8, Issue 2, Page(s) 152–161

Abstract: Atherosclerosis is a major cause of coronary artery disease and stroke. A massive and new type of data has finally arrived in the field of atherosclerosis: single cell RNA sequencing (scRNAseq). Recently, scRNAseq has been successfully applied to the ... ...

Abstract	Atherosclerosis is a major cause of coronary artery disease and stroke. A massive and new type of data has finally arrived in the field of atherosclerosis: single cell RNA sequencing (scRNAseq). Recently, scRNAseq has been successfully applied to the study of atherosclerosis to identify previously uncharacterized cell populations. scRNAseq is an effective approach to evaluate heterogeneous cell populations by measuring the transcriptomic profiles at the single cell level. Besides the studies of atherosclerosis, scRNAseq is being employed in various areas of biology, including cancer research and organ development. In order to analyze these new massive datasets, various analytic approaches have been developed. This review aims to enhance the understanding of this new technology by exploring how the single cell transcriptome has been applied to the study of atherosclerosis and further discuss potential analysis of using scRNAseq.
Language	English
Publishing date	2019-07-30
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	3016001-7
ISSN	2288-2561 ; 2287-2892
ISSN (online)	2288-2561
ISSN	2287-2892
DOI	10.12997/jla.2019.8.2.152
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Article ; Online: VeTra: a tool for trajectory inference based on RNA velocity.

Weng, Guangzheng / Kim, Junil / Won, Kyoung Jae

Bioinformatics (Oxford, England)

2021 Volume 37, Issue 20, Page(s) 3509–3513

Abstract: Motivation: Trajectory inference (TI) for single cell RNA sequencing (scRNAseq) data is a powerful approach to interpret dynamic cellular processes such as cell cycle and development. Still, however, accurate inference of trajectory is challenging. ... ...

Abstract	Motivation: Trajectory inference (TI) for single cell RNA sequencing (scRNAseq) data is a powerful approach to interpret dynamic cellular processes such as cell cycle and development. Still, however, accurate inference of trajectory is challenging. Recent development of RNA velocity provides an approach to visualize cell state transition without relying on prior knowledge. Results: To perform TI and group cells based on RNA velocity we developed VeTra. By applying cosine similarity and merging weakly connected components, VeTra identifies cell groups from the direction of cell transition. Besides, VeTra suggests key regulators from the inferred trajectory. VeTra is a useful tool for TI and subsequent analysis. Availability and implementation: The Vetra is available at https://github.com/wgzgithub/VeTra. Supplementary information: Supplementary data are available at Bioinformatics online.
Language	English
Publishing date	2021-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btab364
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Zs.A 2374: Show issues

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Article ; Online: Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.

Rungratanawanich, Wiramon / Ballway, Jacob W / Wang, Xin / Won, Kyoung-Jae / Hardwick, James P / Song, Byoung-Joon

Pharmacology & therapeutics

2023 Volume 251, Page(s) 108547

Abstract: Epigenetic regulation is a process that takes place through adaptive cellular pathways influenced by environmental factors and metabolic changes to modulate gene activity with heritable phenotypic variations without altering the DNA sequences of many ... ...

Abstract	Epigenetic regulation is a process that takes place through adaptive cellular pathways influenced by environmental factors and metabolic changes to modulate gene activity with heritable phenotypic variations without altering the DNA sequences of many target genes. Epigenetic regulation can be facilitated by diverse mechanisms: many different types of post-translational modifications (PTMs) of histone and non-histone nuclear proteins, DNA methylation, altered levels of noncoding RNAs, incorporation of histone variants, nucleosomal positioning, chromatin remodeling, etc. These factors modulate chromatin structure and stability with or without the involvement of metabolic products, depending on the cellular context of target cells or environmental stimuli, such as intake of alcohol (ethanol) or Western-style high-fat diets. Alterations of epigenetics have been actively studied, since they are frequently associated with multiple disease states. Consequently, explorations of epigenetic regulation have recently shed light on the pathogenesis and progression of alcohol-associated disorders. In this review, we highlight the roles of various types of PTMs, including less-characterized modifications of nuclear histone and non-histone proteins, in the epigenetic regulation of alcohol-associated liver disease (ALD) and other disorders. We also describe challenges in characterizing specific PTMs and suggest future opportunities for basic and translational research to prevent or treat ALD and many other disease states.
MeSH term(s)	Humans ; Histones/metabolism ; Epigenesis, Genetic ; Protein Processing, Post-Translational ; DNA Methylation ; Liver Diseases, Alcoholic/genetics ; Ethanol
Chemical Substances	Histones ; Ethanol (3K9958V90M)
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2023.108547
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Zs.A 1183: Show issues

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Article ; Online: Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation.

Lien, Yu-Chin / Won, Kyoung-Jae / Simmons, Rebecca A

Endocrinology

2020 Volume 161, Issue 12

Abstract: Pancreatic β-cell dysfunction and reduced insulin secretion play a key role in the pathogenesis of diabetes. Fetal and neonatal islets are functionally immature and have blunted glucose responsiveness and decreased insulin secretion in response to ... ...

Abstract	Pancreatic β-cell dysfunction and reduced insulin secretion play a key role in the pathogenesis of diabetes. Fetal and neonatal islets are functionally immature and have blunted glucose responsiveness and decreased insulin secretion in response to stimuli and are far more proliferative. However, the mechanisms underlying functional immaturity are not well understood. Pancreatic islets are composed of a mixture of different cell types, and the microenvironment of islets and interactions between these cell types are critical for β-cell development and maturation. RNA sequencing and quantitative proteomic data from intact islets isolated from fetal (embryonic day 19) and 2-week-old Sprague-Dawley rats were integrated to compare their gene and protein expression profiles. Ingenuity Pathway Analysis (IPA) was also applied to elucidate pathways and upstream regulators modulating functional maturation of islets. By integrating transcriptome and proteomic data, 917 differentially expressed genes/proteins were identified with a false discovery rate of less than 0.05. A total of 411 and 506 of them were upregulated and downregulated in the 2-week-old islets, respectively. IPA revealed novel critical pathways associated with functional maturation of islets, such as AMPK (adenosine monophosphate-activated protein kinase) and aryl hydrocarbon receptor signaling, as well as the importance of lipid homeostasis/signaling and neuronal function. Furthermore, we also identified many proteins enriched either in fetal or 2-week-old islets related to extracellular matrix and cell communication, suggesting that these pathways play critical roles in islet maturation. Our present study identified novel pathways for mature islet function in addition to confirming previously reported mechanisms, and provided new mechanistic insights for future research on diabetes prevention and treatment.
MeSH term(s)	Animals ; Databases, Protein ; Gene Expression Profiling ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/growth & development ; Islets of Langerhans/metabolism ; Proteome ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/physiology ; Transcriptome
Chemical Substances	Proteome
Language	English
Publishing date	2020-10-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqaa187
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Uh III Zs.72: Show issues

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Article ; Online: SHARP: hyperfast and accurate processing of single-cell RNA-seq data via ensemble random projection.

Wan, Shibiao / Kim, Junil / Won, Kyoung Jae

Genome research

2020 Volume 30, Issue 2, Page(s) 205–213

Abstract: To process large-scale single-cell RNA-sequencing (scRNA-seq) data effectively without excessive distortion during dimension reduction, we present SHARP, an ensemble random projection-based algorithm that is scalable to clustering 10 million cells. ... ...

Abstract	To process large-scale single-cell RNA-sequencing (scRNA-seq) data effectively without excessive distortion during dimension reduction, we present SHARP, an ensemble random projection-based algorithm that is scalable to clustering 10 million cells. Comprehensive benchmarking tests on 17 public scRNA-seq data sets show that SHARP outperforms existing methods in terms of speed and accuracy. Particularly, for large-size data sets (more than 40,000 cells), SHARP runs faster than other competitors while maintaining high clustering accuracy and robustness. To the best of our knowledge, SHARP is the only R-based tool that is scalable to clustering scRNA-seq data with 10 million cells.
MeSH term(s)	Algorithms ; Cluster Analysis ; Gene Expression Profiling ; Humans ; RNA/classification ; RNA/genetics ; RNA-Seq ; Sequence Analysis, RNA ; Single-Cell Analysis ; Software ; Transcriptome/genetics ; Whole Exome Sequencing
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2020-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.254557.119
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 8: Show issues

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Article ; Online: Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition.

Kim, Dongha / Kim, Junil / Yu, Young Suk / Kim, Yong Ryoul / Baek, Sung Hee / Won, Kyoung-Jae

Nucleic acids research

2022 Volume 50, Issue 13, Page(s) 7298–7309

Abstract: Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways ... ...

Abstract	Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.
MeSH term(s)	Activating Transcription Factor 4/metabolism ; Amino Acids/genetics ; Amino Acids/metabolism ; Animals ; Autophagy/genetics ; CCAAT-Enhancer-Binding Proteins/metabolism ; Epigenesis, Genetic ; Fibroblasts/metabolism ; Mice ; Single-Cell Analysis ; Transcriptome
Chemical Substances	Amino Acids ; CCAAT-Enhancer-Binding Proteins ; CCAAT-enhancer-binding protein-gamma ; Activating Transcription Factor 4 (145891-90-3)
Language	English
Publishing date	2022-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac593
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Zs.A 1067: Show issues

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Article ; Online: Vesalius: high-resolution in silico anatomization of spatial transcriptomic data using image analysis.

Martin, Patrick C N / Kim, Hyobin / Lövkvist, Cecilia / Hong, Byung-Woo / Won, Kyoung Jae

Molecular systems biology

2022 Volume 18, Issue 9, Page(s) e11080

Abstract: Characterization of tissue architecture promises to deliver insights into development, cell communication, and disease. In silico spatial domain retrieval methods have been developed for spatial transcriptomics (ST) data assuming transcriptional ... ...

Abstract	Characterization of tissue architecture promises to deliver insights into development, cell communication, and disease. In silico spatial domain retrieval methods have been developed for spatial transcriptomics (ST) data assuming transcriptional similarity of neighboring barcodes. However, domain retrieval approaches with this assumption cannot work in complex tissues composed of multiple cell types. This task becomes especially challenging in cellular resolution ST methods. We developed Vesalius to decipher tissue anatomy from ST data by applying image processing technology. Vesalius uniquely detected territories composed of multiple cell types and successfully recovered tissue structures in high-resolution ST data including in mouse brain, embryo, liver, and colon. Utilizing this tissue architecture, Vesalius identified tissue morphology-specific gene expression and regional specific gene expression changes for astrocytes, interneuron, oligodendrocytes, and entorhinal cells in the mouse brain.
MeSH term(s)	Animals ; Mice ; Transcriptome/genetics
Language	English
Publishing date	2022-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193510-5
ISSN	1744-4292 ; 1744-4292
ISSN (online)	1744-4292
ISSN	1744-4292
DOI	10.15252/msb.202211080
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Article ; Online: Inter and transgenerational impact of H3K4 methylation in neuronal homeostasis.

Abay-Nørgaard, Steffen / Tapia, Marta Cecylia / Zeijdner, Mandoh / Kim, Jeonghwan Henry / Won, Kyoung Jae / Porse, Bo / Salcini, Anna Elisabetta

Life science alliance

2023 Volume 6, Issue 8

Abstract: Epigenetic marks and associated traits can be transmitted for one or more generations, phenomena known respectively as inter- or transgenerational epigenetic inheritance. It remains unknown if genetically and conditionally induced aberrant epigenetic ... ...

Abstract	Epigenetic marks and associated traits can be transmitted for one or more generations, phenomena known respectively as inter- or transgenerational epigenetic inheritance. It remains unknown if genetically and conditionally induced aberrant epigenetic states can influence the development of the nervous system across generations. Here, we show, using
MeSH term(s)	Animals ; Methylation ; Caenorhabditis elegans/genetics ; Epigenome ; Epigenomics ; Homeostasis/genetics
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202301970
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