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Article ; Online: Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome

Hyunjin Yoo / Hyeonwoo La / Chanhyeok Park / Seonho Yoo / Hyeonji Lee / Hyuk Song / Jeong Tae Do / Youngsok Choi / Kwonho Hong

Frontiers in Cell and Developmental Biology, Vol

2023 Volume 11

Abstract: Epigenetic mechanisms are mandatory for endothelial called lymphangioblasts during cardiovascular development. Dot1l-mediated gene transcription in mice is essential for the development and function of lymphatic ECs (LECs). The role of Dot1l in the ... ...

Abstract	Epigenetic mechanisms are mandatory for endothelial called lymphangioblasts during cardiovascular development. Dot1l-mediated gene transcription in mice is essential for the development and function of lymphatic ECs (LECs). The role of Dot1l in the development and function of blood ECs blood endothelial cells is unclear. RNA-seq datasets from Dot1l-depleted or -overexpressing BECs and LECs were used to comprehensively analyze regulatory networks of gene transcription and pathways. Dot1l depletion in BECs changed the expression of genes involved in cell-to-cell adhesion and immunity-related biological processes. Dot1l overexpression modified the expression of genes involved in different types of cell-to-cell adhesion and angiogenesis-related biological processes. Genes involved in specific tissue development-related biological pathways were altered in Dot1l-depleted BECs and LECs. Dot1l overexpression altered ion transportation-related genes in BECs and immune response regulation-related genes in LECs. Importantly, Dot1l overexpression in BECs led to the expression of genes related to the angiogenesis and increased expression of MAPK signaling pathways related was found in both Dot1l-overexpressing BECs and LECs. Therefore, our integrated analyses of transcriptomics in Dot1l-depleted and Dot1l-overexpressed ECs demonstrate the unique transcriptomic program of ECs and the differential functions of Dot1l in the regulation of gene transcription in BECs and LECs.
Keywords	blood endothelial cell ; lymphatic endothelial cell ; epigenetics ; DOT1l ; transcriptional regulation ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Germ Cell Derivation from Pluripotent Stem Cells for Understanding In Vitro Gametogenesis

Tae-Kyung Hong / Jae-Hoon Song / So-Been Lee / Jeong-Tae Do

Cells, Vol 10, Iss 1889, p

2021 Volume 1889

Abstract: Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising ...

Abstract	Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells. Here, we review the recent advances in in vitro male and female germ cell derivation from PSCs and discuss how this technique is used to understand the biological mechanism of gamete development and gain insight into its application in infertility.
Keywords	germ cell ; gametogenesis ; pluripotent stem cell ; infertility ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Expression and Regulation of CD73 during the Estrous Cycle in Mouse Uterus

Jihyun Lee / Haeun Park / Sohyeon Moon / Jeong-Tae Do / Kwonho Hong / Youngsok Choi

International Journal of Molecular Sciences, Vol 22, Iss 9403, p

2021 Volume 9403

Abstract: Cluster of differentiation 73 (CD73, also known as ecto-5′-nucleotidase) is an enzyme that converts AMP into adenosine. CD73 is a surface enzyme bound to the outside of the plasma membrane expressed in several cells and regulates immunity and ... ...

Abstract	Cluster of differentiation 73 (CD73, also known as ecto-5′-nucleotidase) is an enzyme that converts AMP into adenosine. CD73 is a surface enzyme bound to the outside of the plasma membrane expressed in several cells and regulates immunity and inflammation. In particular, it is known to inhibit T cell-mediated immune responses. However, the regulation of CD73 expression by hormones in the uterus is not yet clearly known. In this study, we investigated the expression of CD73 in ovariectomized mice treated with estrogen or progesterone and its regulation in the mouse uterus during the estrous cycle. The level of CD73 expression was dynamically regulated in the uterus during the estrous cycle. CD73 protein expression was high in proestrus, estrus, and diestrus, whereas it was relatively low in the metestrus stage. Immunofluorescence revealed that CD73 was predominantly expressed in the cytoplasm of the luminal and glandular epithelium and the stroma of the endometrium. The expression of CD73 in ovariectomized mice was gradually increased by progesterone treatment. However, estrogen injection did not affect its expression. Moreover, CD73 expression was increased when estrogen and progesterone were co-administered and was inhibited by the pretreatment of the progesterone receptor antagonist RU486. These findings suggest that the expression of CD73 is dynamically regulated by estrogen and progesterone in the uterine environment, and that there may be a synergistic effect of estrogen and progesterone.
Keywords	CD73 ; ecto-5′-nucleotidase ; uterus ; estrogen ; progesterone ; estrous cycle ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer

Nguyen Xuan Thang / Dong Wook Han / Chanhyeok Park / Hyeonji Lee / Hyeonwoo La / Seonho Yoo / Heeji Lee / Sang Jun Uhm / Hyuk Song / Jeong Tae Do / Kyoung Sik Park / Youngsok Choi / Kwonho Hong

Frontiers in Cell and Developmental Biology, Vol

2023 Volume 11

Abstract: The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in ...

Abstract	The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in cancer etiology, especially in breast cancer, remains unclear. In the present study, we have performed a weighted gene co-expression network analysis (WCGNA) to investigate links between INO80 expression and breast cancer sub-classification and progression. Our analysis revealed that INO80 repression is associated with differential responsiveness of estrogen receptors (ERs) depending upon breast cancer subtype, ER networks, and increased risk of breast carcinogenesis. To determine whether INO80 loss induces breast tumors, a conditional INO80-knockout (INO80 cKO) mouse model was generated using the Cre-loxP system. Phenotypic characterization revealed that INO80 cKO led to reduced branching and length of the mammary ducts at all stages. However, the INO80 cKO mouse model had unaltered lumen morphology and failed to spontaneously induce tumorigenesis in mammary gland tissue. Therefore, our study suggests that the aberrant function of INO80 is potentially associated with breast cancer by modulating gene expression. INO80 mutation alone is insufficient for breast tumorigenesis.
Keywords	mammary gland development ; breast cancer ; INO80 ; transcriptional regulation ; estrogen ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder

Sang Hoon Yoon / Joonhyuk Choi / Won Ji Lee / Jeong Tae Do

Journal of Clinical Medicine, Vol 9, Iss 966, p

2020 Volume 966

Abstract: Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities and interests. Environmental factors, ...

Abstract	Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities and interests. Environmental factors, such as viral infection, parental age, and zinc deficiency, can be plausible contributors to ASD susceptibility. As ASD is highly heritable, genetic risk factors involved in neurodevelopment, neural communication, and social interaction provide important clues in explaining the etiology of ASD. Accumulated evidence also shows an important role of epigenetic factors, such as DNA methylation, histone modification, and noncoding RNA, in ASD etiology. In this review, we compiled the research published to date and described the genetic and epigenetic epidemiology together with environmental risk factors underlying the etiology of the different phenotypes of ASD.
Keywords	autism spectrum disorder ; genetic ; epigenetic ; etiology ; Medicine ; R
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mitochondrial Dynamics in Stem Cells and Differentiation

Bong Jong Seo / Sang Hoon Yoon / Jeong Tae Do

International Journal of Molecular Sciences, Vol 19, Iss 12, p

2018 Volume 3893

Abstract: Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is adenosine triphosphate (ATP) production; however, they are additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, ... ...

Abstract	Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is adenosine triphosphate (ATP) production; however, they are additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, proliferation, differentiation, reprogramming, and aging. The change in mitochondrial morphology is closely related to the functionality of mitochondria. Normal mitochondrial dynamics are critical for cellular function, embryonic development, and tissue formation. Thus, defects in proteins involved in mitochondrial dynamics that control mitochondrial fusion and fission can affect cellular differentiation, proliferation, cellular reprogramming, and aging. Here, we review the processes and proteins involved in mitochondrial dynamics and their various associated cellular phenomena.
Keywords	mitochondria ; mitochondrial dynamics ; fusion ; fission ; pluripotency ; differentiation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficient Generation of Neural Stem Cells from Embryonic Stem Cells Using a Three-Dimensional Differentiation System

Sang-Hoon Yoon / Mi-Rae Bae / Hyeonwoo La / Hyuk Song / Kwonho Hong / Jeong-Tae Do

International Journal of Molecular Sciences, Vol 22, Iss 8322, p

2021 Volume 8322

Abstract: Mouse embryonic stem cells (ESCs) are useful tools for studying early embryonic development and tissue formation in mammals. Since neural lineage differentiation is a major subject of organogenesis, the development of efficient techniques to induce ... ...

Abstract	Mouse embryonic stem cells (ESCs) are useful tools for studying early embryonic development and tissue formation in mammals. Since neural lineage differentiation is a major subject of organogenesis, the development of efficient techniques to induce neural stem cells (NSCs) from pluripotent stem cells must be preceded. However, the currently available NSC differentiation methods are complicated and time consuming. This study aimed to propose an efficient method for the derivation of NSCs from mouse ESCs; early neural lineage commitment was achieved using a three-dimensional (3D) culture system, followed by a two-dimensional (2D) NSC derivation. To select early neural lineage cell types during differentiation, Sox1 -GFP transgenic ESCs were used. They were differentiated into early neural lineage, forming spherical aggregates, which were subsequently picked for the establishment of 2D NSCs. The latter showed a morphology similar to that of brain-derived NSCs and expressed NSC markers, Musashi, Nestin, N-cadherin, and Sox2. Moreover, the NSCs could differentiate into three subtypes of neural lineages, neurons, astrocytes, and oligodendrocytes. The results together suggested that ESCs could efficiently differentiate into tripotent NSCs through specification in 3D culture (for approximately 10 days) followed by 2D culture (for seven days).
Keywords	embryonic stem cells ; neural differentiation ; 3D culture ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cellular Reprogramming Using Protein and Cell-Penetrating Peptides

Bong Jong Seo / Yean Ju Hong / Jeong Tae Do

International Journal of Molecular Sciences, Vol 18, Iss 3, p

2017 Volume 552

Abstract: Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear ... ...

Abstract	Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear transfer technology to direct reprogramming using defined factors, or induced pluripotent stem cells (iPSCs). Considering the ethical issues and efficiency, iPSCs are thought to be one of the most promising stem cells for cell therapy. Induced pluripotent stem cells can be generated by transduction with a virus, plasmid, RNA, or protein. Herein, we provide an overview of the current technology for iPSC generation and describe protein-based transduction technology in detail.
Keywords	cell penetrating peptide ; reprogramming ; protein ; iPSCs ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2017-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: INO80 Is Required for the Cell Cycle Control, Survival, and Differentiation of Mouse ESCs by Transcriptional Regulation

Seonho Yoo / Eun Joo Lee / Nguyen Xuan Thang / Hyeonwoo La / Hyeonji Lee / Chanhyeok Park / Dong Wook Han / Sang Jun Uhm / Hyuk Song / Jeong Tae Do / Youngsok Choi / Kwonho Hong

International Journal of Molecular Sciences, Vol 23, Iss 15402, p

2022 Volume 15402

Abstract: Precise regulation of the cell cycle of embryonic stem cells (ESCs) is critical for their self-maintenance and differentiation. The cell cycle of ESCs differs from that of somatic cells and is different depending on the cell culture conditions. However, ... ...

Abstract	Precise regulation of the cell cycle of embryonic stem cells (ESCs) is critical for their self-maintenance and differentiation. The cell cycle of ESCs differs from that of somatic cells and is different depending on the cell culture conditions. However, the cell cycle regulation in ESCs via epigenetic mechanisms remains unclear. Here, we showed that the ATP-dependent chromatin remodeler Ino80 regulates the cell cycle genes in ESCs under primed conditions. Ino80 loss led to a significantly extended length of the G1-phase in ESCs grown under primed culture conditions. Ino80 directly bound to the transcription start site and regulated the expression of cell cycle-related genes. Furthermore, Ino80 loss induced cell apoptosis. However, the regulatory mechanism of Ino80 in differentiating ESC cycle slightly differed; an extended S-phase was detected in differentiating inducible Ino80 knockout ESCs. RNA-seq analysis of differentiating ESCs revealed that the expression of genes associated with organ development cell cycle is persistently altered in Ino80 knockout cells, suggesting that cell cycle regulation by Ino80 is not limited to undifferentiated ESCs. Therefore, our study establishes the function of Ino80 in ESC cycle via transcriptional regulation, at least partly. Moreover, this Ino80 function may be universal to other cell types.
Keywords	ES cell ; Ino80 ; cell cycle ; apoptosis ; differentiation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of Transcriptional and Epigenetic Regulation in Lymphatic Endothelial Cell Development

Hyeonwoo La / Hyunjin Yoo / Young Bin Park / Nguyen Xuan Thang / Chanhyeok Park / Seonho Yoo / Hyeonji Lee / Youngsok Choi / Hyuk Song / Jeong Tae Do / Kwonho Hong

Cells, Vol 11, Iss 1692, p

2022 Volume 1692

Abstract: The lymphatic system is critical for maintaining the homeostasis of lipids and interstitial fluid and regulating the immune cell development and functions. Developmental anomaly-induced lymphatic dysfunction is associated with various pathological ... ...

Abstract	The lymphatic system is critical for maintaining the homeostasis of lipids and interstitial fluid and regulating the immune cell development and functions. Developmental anomaly-induced lymphatic dysfunction is associated with various pathological conditions, including lymphedema, inflammation, and cancer. Most lymphatic endothelial cells (LECs) are derived from a subset of endothelial cells in the cardinal vein. However, recent studies have reported that the developmental origin of LECs is heterogeneous. Multiple regulatory mechanisms, including those mediated by signaling pathways, transcription factors, and epigenetic pathways, are involved in lymphatic development and functions. Recent studies have demonstrated that the epigenetic regulation of transcription is critical for embryonic LEC development and functions. In addition to the chromatin structures, epigenetic modifications may modulate transcriptional signatures during the development or differentiation of LECs. Therefore, the understanding of the epigenetic mechanisms involved in the development and function of the lymphatic system can aid in the management of various congenital or acquired lymphatic disorders. Future studies must determine the role of other epigenetic factors and changes in mammalian lymphatic development and function. Here, the recent findings on key factors involved in the development of the lymphatic system and their epigenetic regulation, LEC origins from different organs, and lymphatic diseases are reviewed.
Keywords	epigenetics ; transcription factor ; lymphatic endothelium ; lymphatic disease ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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