• 제목/요약/키워드: Self-renewal

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스타틴 그리고 배아줄기세포에서의 작용 (Statins and Their Effects on Embryonic Stem Cells)

  • 이미희;한용만;조이숙
    • 한국발생생물학회지:발생과생식
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    • 제11권2호
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    • pp.59-66
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    • 2007
  • 배아줄기세포를 이용한 치료법 개발을 위해서는 배아줄기세포의 자가재생산 및 분화과정을 조절하는 분자적 기전을 이해하는 것이 매우 중요하다. 지질합성경로(Mevalonate pathway)에 작용하는 HMG-CoA 환원효소(Hydroxymethylglutaryl-coenzyme A reductase)의 억제제인 스타틴은 콜레스테롤 저하제로 잘 알려져 있으며, 콜레스테롤 이외에 단백질 isoprenylation의 기질로 작용하는 아이소프레노이드(Isoprenoids)(Farnesyl pyrophosphate(FPP), Geranylgeranyl pyrophosphate(GGPP))의 생성을 억제하는 효능을 가지고 있다. 스타틴에 의해 매개되는 표적단백질의 isoprenylation 억제는 다양한 세포내 신호전달과정에 영향을 미치게 되며, 결과적으로 세포기능을 조절하는데 핵심적인 역할을 하게 된다. 스타틴이 첨가된 배양배지에서 배양된 배아줄기세포는 자가재생산능이 억제되고 분화가 촉진되는데, 특히 지방/골세포 직계열로의 분화가 촉진된다. 배아줄기세포에서의 스타틴의 효과 및 작용기전에 대한 이해가 아직은 미비한 수준이나, 최근 우리 연구팀에서는 스타틴이 콜레스테롤 작용과는 무관하게 RhoA G-단백질의 세포내 분포 및 활성을 억제함으로써 배아 줄기세포의 자가재생산능을 억제하고 있음을 규명하였다. 스타틴 다면효과와 그 작용에 대한 이해는 배아줄기세포의 미분화 및 분화상태를 조절하는데 관여하는 분자적 조절기전을 이해하는데 중요한 모델이 될 수 있을 것으로 추정된다.

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LIMIT THEOREMS FOR HAWKES PROCESSES WITH UNIFORM IMMIGRANTS

  • Seol, Youngsoo
    • 대한수학회지
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    • 제56권4호
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    • pp.935-946
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    • 2019
  • Hawkes process is a self-exciting simple point process with clustering effect whose jump rate depends on its entire past history. We consider Hawkes processes with uniform immigrants which is a special case of the Hawkes processes with renewal immigrants. We study the limit theorems for Hawkes processes with uniform immigrants. In particular, we obtain a law of large number, a central limit theorem, and a large deviation principle.

대순진리회 목적(目的)에 관한 연구 (Examining the Object of Daesoonjinrihoe)

  • 유병무
    • 대순사상논총
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    • 제26집
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    • pp.183-214
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    • 2016
  • The purpose of this study is to promote the understanding of the objective of Daesoon Thought through 'examining the Objectives of Daesoonjinrihoe.' The objective of Daesoon thought was set when Kang Jeungsan Sangje descended to human world, upon the plea of divine sages, buddhas, and bodhisattvas, and determined to save the world and relieve people far and wide. For building an Earthly Paradise with Daesoon thought, Sangje carried out the great work of Reordering of the Universe for nine years and passed into heaven. Cho Jeongsan Doju, who received the heavenly religious orthodox through divine revelation from Sangje, served the late will of Sangje and established Main Tenets, Creeds, and objective of Daesoon thought. The objective set by Doju was continued to Park Wudang Dojeon and formed the Objectives of Daesoonjinrihoe. The Objectives of Daesoonjinrihoe consist of three sets of objectives in sequential order, which are related in organic, mutual beneficient, and integrative with one another. The Objectives starts from individual cultivation and expand into worldly reformation: 1)one's Spiritual transformation through Guarding against self-deception 2)Renewal of human beings through Realizing Earthly Immortality 3)Opening of new world through Building of Earthly Paradise. Also, in these Objectives of Daesoonjinrihoe, Three Realms of Heaven, Earth, and Humanity keep close relations to enter into new world. These Objectives are based on the 'thought of mutual beneficence' and are realized with Daesoon thought, which is the Dao of 'Crowned King' that goes beyond the previous thoughts of Confucianism, Buddhism and Taoism. Objectives of Daesoonjinrihoe have following details in each objective as following; (1) 'Guarding against self-deception-Spiritual Transformation' is for human nature. In Daesoon thought, human has the potential to restore conscience, which is true nature, and return to undefiled essence by 'guarding against self-deception'. In other words, it views that one can reach into the stage of spiritual alignment with the Dao once he recovers conscience through cultivation of Daesoonjinrihoe based on the idea of 'Guarding against self-deception'. (2) 'Realizing Earthly Immortality-Renewal of human beings' is for ideal human character. 'Realizing Earthly Immortality' in Daesoon Thought indicates the advent of ideal human beings called 'Dotong gunja'(virtuous beings who are aligned with the Dao). They are leaders who integrate politics and religion in helping people to renew themselves and make the world into Earthly Paradise. (3) 'Building an Earthly Paradise-Opening of new world' is for ideal society. Daesoon thought aims to making a peaceful world by creating an ideal society of heaven on this earth. Park Wudang Dojeon, who led Daesoonjinrihoe, emphasized the importance of Three Basic Activities: Spreading of Sangje's virtue, Edification, and Cultivation: and Three Major Activities: Aid and charity, Social welfare, and Education. Dojeon said "One should make effort to reach the utmost goodness through enlightening their bright virtue and cultivating their talent virtue." In this words, he made clear that the Objectives of Daesoonjinrihoe can be realized when people enlighten their bright virtue and cultivate themselves with their talent virtue. In conclusion, the Objectives of Daesoon thought were clarified of their meanings by Sangje, established into laws by Doju, and actualized by Dojoen in various activities of Daesoonjinrihoe.

miRNA-222 Modulates Differentiation of Mouse Embryonic Stem Cells

  • Ahn, Hee-Jin;Jung, Jee-Eun;Park, Kyung-Soon
    • 한국발생생물학회지:발생과생식
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    • 제15권4호
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    • pp.331-338
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    • 2011
  • MicroRNAs (miRNAs) function as a key regulator of diverse cellular functions. To find out novel miRNAs that promote the differentiation of mouse embryonic stem cells (mESCs), we compared the miRNAs expression profiles of mESCs under self-renewal vs. differentiation states. We noticed that miR-222 was highly expressed during the differentiation of mESCs. Quantitative RT-PCR analysis revealed that expression of miR-222 was up-regulated during the embryonic bodies formation and retinoic acid -dependent differentiation. When miR-222 was suppressed by antogomiR-222, the differentiation of mESCs was delayed compared to control. Self-renewal marker expression or cell proliferation was not affected but the expression of lineage specific marker was suppressed by the treatment of miR-222 inhibitor during the differentiation of mESCs. Taken together, these results suggest that miR-222 functions to promote the differentiation of mESCs by regulating expression of differentiation related genes.

MicroRNA-203 As a Stemness Inhibitor of Glioblastoma Stem Cells

  • Deng, Yifan;Zhu, Gang;Luo, Honghai;Zhao, Shiguang
    • Molecules and Cells
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    • 제39권8호
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    • pp.619-624
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    • 2016
  • Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.

Cancer Stem Cells and Stemness Markers in Oral Squamous Cell Carcinomas

  • Patel, Shanaya Saurin;Shah, Kanisha Atul;Shah, Manoj Jashwantbhai;Kothari, Kiran Champaklal;Rawal, Rakesh Mahesh
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권20호
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    • pp.8549-8556
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    • 2014
  • Head and neck squamous cell carcinoma (HNSCC) is one of the world top ten most common cancers with its highest occurrence in the Indian subcontinent and different aggressive and etiological behavioural patterns. The scenario is only getting worst with the 5 year survival rates dropping to 50%, persistent treatment failures and frequent cases of relapse/recurrence. One of the major reasons for these failures is the presence of cancer stem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal and have the ability to differentiate into cells that constitute the bulk of tumours. Notably, recent evidence suggests that cancer stem cells are especially resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. Specific markers for this population have been investigated in HNSCC in the hope of developing a deeper understanding of their role in oral cancer pathogenesis, elucidating novel biomarkers for early diagnosis and newer therapeutic strategies. This review covers the fundamental relevance of almost all the CSC biomarkers established to date with a special emphasis on their impact in the process of oral tumourigenesis and their potential role in improving the diagnosis, prognosis and treatment of OSCC patients.

방사선조사 동물모델 이용 면역기능개선-생약복합물 헤모힘(HemoHIM)개발 (Development of A New Herbal Composition HemoHIM as An Immune-Improving Agent Using Irradiated Animal Models)

  • 조성기
    • 동위원소회보
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    • 제21권4호
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    • pp.38-45
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    • 2006
  • A new herbal composition. HemoHIM, was developed using irradiated animal models and was successfully applied as an immune-improving agent. In a view that the protection and recovery of immune, hematopoietic and self-renewal tissues are essential for radioprotective agents, HemoHIM was developed based on a novel combination of three edible herbs (Angelica Radix, Cnidii Rhizoma. Paeonin Radix) that meet all those requirements. HemoHIM significantly protected the immune and hematopoietic system and enhanced their recovery in y-irradiated mice. For the application of HemoHIM as a health functional food and a supplementary agent for the cancer patients, the efficacy of HemoHIM to improve the immune functions was further evaluated in immune-depressed animals and humans. Animal studies demonstrated that HemoHIM significantly improved the immune functions in cyclophosphamide-treated mice, aged mice, and dexamethasone-treated mice. In human studies, HemoHIM enhanced the immune activity and cytokine secretion in sub-healthy volunteers, and alleviated the severe leukocyre depression in cancer patients during radiation and chemotherapy. Based on these results, HemoHIM was approved by Korea FDA as a material of health functional food for immune function improvement and will be commercially available soon. This case of HemoHIM research and development suggested that irradiated animals can be good models for biological degenerations such as immune depression, self-renewal tissue damage, and aging for the development of biological modulators.

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The Kleisin Subunits of Cohesin Are Involved in the Fate Determination of Embryonic Stem Cells

  • Koh, Young Eun;Choi, Eui-Hwan;Kim, Jung-Woong;Kim, Keun Pil
    • Molecules and Cells
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    • 제45권11호
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    • pp.820-832
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    • 2022
  • As a potential candidate to generate an everlasting cell source to treat various diseases, embryonic stem cells are regarded as a promising therapeutic tool in the regenerative medicine field. Cohesin, a multi-functional complex that controls various cellular activities, plays roles not only in organizing chromosome dynamics but also in controlling transcriptional activities related to self-renewal and differentiation of stem cells. Here, we report a novel role of the α-kleisin subunits of cohesin (RAD21 and REC8) in the maintenance of the balance between these two stem-cell processes. By knocking down REC8, RAD21, or the non-kleisin cohesin subunit SMC3 in mouse embryonic stem cells, we show that reduction in cohesin level impairs their self-renewal. Interestingly, the transcriptomic analysis revealed that knocking down each cohesin subunit enables the differentiation of embryonic stem cells into specific lineages. Specifically, embryonic stem cells in which cohesin subunit RAD21 were knocked down differentiated into cells expressing neural alongside germline lineage markers. Thus, we conclude that cohesin appears to control the fate determination of embryonic stem cells.