자궁 내 배아 착상 환경에 대한 이해

송행석,Song, Haengseok 대한생식의학회 2006 Clinical and Experimental Reproductive Medicine Vol.33 No.3

Regulation of Differentiation Potential of Human Mesenchymal Stem Cells by Intracytoplasmic Delivery of Coactivator-Associated Arginine Methyltransferase 1 Protein Using Cell-Penetrating Peptide

Jo, Junghyun,Song, Haengseok,Park, Sang Gyu,Lee, Soo-Hong,Ko, Jung-Jae,Park, Jong-Hyuk,Jeong, Jaemin,Cheon, Yong-Pil,Lee, Dong Ryul Wiley (John WileySons) 2012 Stem cells Vol.30 No.8

<P>Recent studies suggest that epigenetic modifications, such as DNA methylation and histone modification, can alter the differentiation potential of stem cells or progenitor cells. Specifically, coactivator-associated arginine methyltransferase 1 (CARM1) is known to act as a coactivator for various transcription factors and to regulate gene expression by chromatin remodeling through histone methylation. Here, for the first time, we have used direct protein delivery of CARM1 using cell-penetrating peptide (CPP) to regulate the differentiation potential of human mesenchymal stem cells (hMSCs). Immunofluorescence showed that the CPP-CARM1 protein is successfully delivered into the nuclei of hMSCs. Further experiments using immunofluorescence and Western blotting showed that the delivered CARM1 protein can effectively methylate the arginine 17 residue of histone H3 in both bone marrow (BM)- and adipose-derived (AD)-hMSCs, thus suggesting that the CARM1 protein delivered by the CPP system is biologically active in hMSCs. Chromatin immunoprecipitation (ChIP) assay and genome-wide gene expression profiling supported the result that delivered CARM1 protein can cause chromatin remodeling through histone methylation. Finally, the CPP-CARM1 protein efficiently elevated the differentiation efficiency of BM-hMSCs and AD-hMSCs into adipogenic, osteogenic, and myogenic cell lineages in vitro. Altered expression of critical genes after hMSC differentiation was reconfirmed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Collectively, our results suggest that CPP-CARM1 can elevate the differentiation potential of hMSCs into various cell types, and that this system using CPP is a useful tool for exogenous protein delivery in clinical applications of cell-based therapy.</P>

Etv5, a transcription factor with versatile functions in male reproduction

Eo, Jinwon,Song, Haengseok,Lim, Hyunjung Jade The Korean Society for Reproductive Medicine 2012 Clinical and Experimental Reproductive Medicine Vol.39 No.2

Transcription factors govern diverse aspects of cell growth and differentiation as major switches of gene expression. Etv5, a member of the E26 transformation-specific family of transcription factors, has many stories to share when it comes to reproduction. Etv5 deficient mice show complex infertility phenotypes both in males and females. In males, the infertility phenotype exhibited by Etv5 deficiency is sexually dimorphic, and it involves both somatic cells and germ cells. In $Etv5^{-/-}$ female mice, the problem is more complicated by hormonal involvement. This review synthesizes old and new information on this versatile transcription factor-from the inadvertent discovery of its role in the testes to its newly discovered role in maintaining spermatogonial stem cells.

Melatonin significantly down-regulates long non-coding RNA Cox2 in M1 macrophages stimulated with LPS

Dohyeong Kim,Haengseok Song 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.7

Egr3 exhibits a unique subcellular localization in mouse oocytes during meiotic maturation

Hyejin Shin,Hyunjung Lim,Haengseok Song 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-

The Egr family of zinc finger transcription factors consisting of 4 members (Egr1 to -4) regulates critical genetic programs involved in cellular growth, differentiation, and function. Especially, the critical role for Egr1 in regulating luteinizing hormone responsiveness was demonstrated by using gene-targeted mouse models. Other members of Egr family were shown to be involved in other cellular and developmental processes. To understand if Egr3 is implicated in ovarian functions, we focused on identifying cell type-specific and subcellular localization of Egr3 in cycling mouse ovaries and oocytes. RT-PCR analyses show that Egr3 mRNA is expressed in the mouse ovary and oocytes. By immunofluorescence staining, we observed that Egr3 is weakly expressed in subsets of granulosa cells. Interestingly, Egr3 seems to be co-localized with meiotic spindle in some oocytes in the ovarian section. Therefore, we examined Egr3 localization in MI oocytes cultured in vitro. We confirmed co-localization of Egr3 and microtubule in the mouse oocyte during meiosis I. Egr3 localization is noted around condensing chromosomes during prometaphase I (PMI). At metaphase I (MI) and MII, Egr3 is localized on meiotic spindle and also around each cytosolic microtubule organizing centers (MTOCs) in a punctate pattern. To examine if microtubule is required for correct positioning of Egr3 on this structure, we observed the pattern of Egr3 in oocytes matured under taxol or nocodazole. In taxol-treated oocyte, Egr3 and gamma-tubulin complex are enlarged. In nocodazole-treated oocyte, Egr3 localization on spindle and MTOCs are abolished. Thus, Egr3 localization seems to require the presence of intact microtubule. Collectively, our result shows for the first time that Egr3, a transcription factor, is localized on meiotic spindle of maturing mouse oocytes. The work suggests a novel role for Egr3 as a factor involved in MTOC dynamics during meiosis.

Egr-1 is necessary for fibroblast growth factor-2-induced transcriptional activation of the glial cell line-derived neurotrophic factor in murine astrocytes.

Shin, Soon Young,Song, Haengseok,Kim, Chang Gun,Choi, Yang-Kyu,Lee, Kyoung Sun,Lee, Seung-Jae,Lee, He-Jin,Lim, Yoongho,Lee, Young Han American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.44

<P>Glial cell line-derived neurotrophic factor (Gdnf) promotes neurite outgrowth and survival of neuronal cells, but its transcriptional regulation is poorly understood. Here, we sought to investigate the mechanism underlying fibroblast growth factor-2 (FGF2) induction of Gdnf expression in astrocytes. We found that FGF2 stimulation of rat astrocytes induced expression of Egr-1 at a high level. Sequence analysis of the rat Gdnf gene identified three overlapping Egr-1-binding sites between positions -185 and -163 of the rat Gdnf promoter. Transfection studies using a series of deleted Gdnf promoters revealed that these Egr-1-binding sites are required for maximal activation of the Gdnf promoter by FGF2. Chromatin immunoprecipitation analysis indicated that Egr-1 binds to the Gdnf promoter. Furthermore, the induction of Gdnf expression by FGF2 is strongly attenuated both in C6 glioma cells stably expressing Egr-1-specific small interfering RNA and in primary cultured astrocytes from the Egr-1 knock-out mouse. Additionally, we found that stimulation of the ERK and JNK pathways by FGF2 is functionally linked to Gdnf expression through the induction of Egr-1. These data demonstrate that FGF2-induced Gdnf expression is mediated by the induction of Egr-1 through activation of the ERK and JNK/Elk-1 signaling pathways.</P>

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

Kim, Jin Yeong,Song, Haengseok,Kim, Hyunjoo,Kang, Hee Jung,Jun, Jin Hyun,Hong, Sung Ran,Koong, Mi Kyoung,Kim, In Sun Issued for the Endocrine Society by the Williams W 2009 The Journal of clinical endocrinology & metabolism Vol.94 No.4

<P>CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders. OBJECTIVE: The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method. DESIGN: Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues. SETTING: This study was performed at a university hospital laboratory. Patients: This study comprised 12 regularly cycling women and 12 PCOS patients. MAIN OUTCOME MEASURE: Dysregulated signaling pathways in PCOSE were identified as a gene set. RESULTS: Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE. CONCLUSIONS: Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.</P>

Platelet-rich plasma treatment in patients with refractory thin endometrium and recurrent implantation failure: A comprehensive review

Kim, Min Kyoung,Song, Haengseok,Lyu, Sang Woo,Lee, Woo Sik The Korean Society for Reproductive Medicine 2022 Clinical and Experimental Reproductive Medicine Vol.49 No.3

Refractory thin endometrium and recurrent implantation failure are among the most challenging infertility-related factors hindering successful pregnancy. Several adjuvant therapies have been investigated to increase endometrial thickness and the pregnancy rate, but the treatment effect is still minimal, and for many patients, these treatment methods can be quite costly and difficult to approach. Platelet-rich plasma (PRP) is an autologous concentration of platelets in plasma and has recently been elucidated as a better treatment option for these patients. PRP is rich in cytokines and growth factors, which are suggested to exert a regenerative effect at the level of the injured tissue. Another advantage of PRP is that it is easily obtained from the patient's own blood. We aimed to review the recent findings of PRP therapy used for patients with refractory thin endometrium and recurrent implantation failure.

Gestational Diabetes Affects the Growth and Functions of Perivascular Stem Cells

An, Borim,Kim, Eunbi,Song, Haengseok,Ha, Kwon-Soo,Han, Eun-Taek,Park, Won Sun,Ahn, Tae Gyu,Yang, Se-Ran,Na, Sunghun,Hong, Seok-Ho Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.6

Gestational diabetes mellitus (GDM), one of the common metabolic disorders of pregnancy, leads to functional alterations in various cells including stem cells as well as some abnormalities in fetal development. Perivascular stem cells (PVCs) have gained more attention in recent years, for the treatment of various diseases. However, the effect of GDM on PVC function has not been investigated. In our study, we isolated PVCs from umbilical cord of normal pregnant women and GDM patients and compared their phenotypes and function. There is no significant difference in phenotypic expression, response to bFGF exposure and adipogenic differentiation capacity between normal (N)-PVCs and GDM-PVCs. However, when compared with N-PVCs, early passage GDM-PVCs displayed decreased initial rates of cell yield and proliferation as well as a reduced ability to promote wound closure. These results suggest that maternal metabolic dysregulation during gestation can alter the function of endogenous multipotent stem cells, which may impact their therapeutic effectiveness.

Egr1 is a critical transcription factor to mediate estrogen responses in mouse uterus

Jung Ah Yoon,Haengseok Song 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-

The Egr family of zinc finger transcription factors consisting of 4 members (Egr1 to Egr4) regulates critical genetic programs involved in cellular growth, differentiation, and function. They are co-ex-pressed in many different tissues, suggesting that they may have some redundant functions. While it is clear that estrogen regulates Egr1 in estrogen sensitive breast cancer cells, function of Egr1 and mechanisms by which estrogen (E2) and/or progesterone (P4) regulates Egr1 in uterus still remain unexplored. Thus, we have examined regulatory mechanisms by which Egr1 is regulated in the uterus and abnormal uterine phenotypes of Egr1(-/-) mice. Eight-week-old female mice were ovariectomized (OVX) and rested for a week. Uteri of OVX mice treated with various concentrations of E2 and/or other hormones were collected at 2 h after hormone treatment unless otherwise indicated. ICI 182,780 [estrogen receptor (ER) antagonist] or RU486 [progesterone receptor (PR) antagonist] was injected to OVX mice 30 min prior to hormone treatments. OVX Egr1(+/+) and Egr1(-/-) mice were treated with E2 and/or P4 to examine expression patterns of genes important for estrogen responses, and steroid hormone-induced cell proliferation in the uterus. Collected uteri were utilized for RT-PCR, realtime RT-PCR, Western blotting and histological analyses. Egr1 mRNA was rapidly induced with the highest level at 2h after E2 treatment and gradually deceased to basal levels at 12 h. Pretreatment of ICI 182,780 significantly reduced E2-induced increase of Egr1. However, an agonist for GPR30, a membrane estrogen receptor failed to induce mRNA expression of Egr1, suggesting that E2-dependent Egr1 transcription is mainly regulated via nuclear estrogen receptor, ER. P4 effectively dampened E2-dependent Egr1 transcription and its antagonistic effects were partially interfered with RU486 pretreatment. Histological analyses with BrdU incorporation experiments showed that vascular permeability (an early estrogen response) but not cell proliferation (a late response) was significantly impaired in the uteri of E2 treated OVX Egr1(-/-) mice. Interestingly, some genes involved in early estrogen responses such as Bip and HIF-1a but not those in late responses are dysregulated in uteri of Egr1(-/-) mice. Collectively, our results show that E2 transiently induces Egr1 via activation of nuclear ER. P4 antagonizes E2-dependent Egr1 regulation via PR. Impaired early estrogenic responses in Egr1(-/-) uteri could be due to aberrant gene expression affected by loss of Egr1 which act as a master regulator of estrogen actions in the uterus.-ex