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関連する概念動画

Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

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Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
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Negative Regulator Molecules01:23

Negative Regulator Molecules

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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The Cell Cycle Control System01:28

The Cell Cycle Control System

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The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
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The Cell Cycle Control System02:11

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The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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細胞サイクル経路による多能状態解消の決定的制限

Kevin Andrew Uy Gonzales1, Hongqing Liang2, Yee-Siang Lim2

  • 1Stem Cell and Regenerative Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.

Cell
|August 2, 2015
PubMed
まとめ

人間の胚性幹細胞 (hESCs) は,多能性状態溶解 (PSD) による分化中に多能性を失います. 細胞サイクル進行,特にSとG2段階は,PSDを積極的に抑制し,細胞サイクルと多能性の間の固有のリンクを明らかにします.

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科学分野:

  • 幹細胞生物学
  • 細胞循環の調節
  • エピジェネティクス

背景:

  • 人間の胚性幹細胞 (hESC) は多能性を持ち,様々な細胞タイプに分化する能力を持っています.
  • 多能性は,多能状態溶解 (PSD) と呼ばれるプロセスを経て,微分化中に失われます.
  • PSDを規制する規制ネットワークは完全に理解されていません.

研究 の 目的:

  • 人間の胚性幹細胞 (hESC) の多能性状態解消 (PSD) の主要な調節体を特定する.
  • 細胞周期が多能性を調節する役割を調査する.
  • 細胞サイクルの進行が分化開始にどのように影響するかを理解する.

主な方法:

  • 高通量RNA干渉 (RNAi) スクリーンで,PSDを調節する遺伝子を特定する.
  • 異なる差別化条件が採用された.
  • 細胞周期相特有の効果を研究するために,遺伝的および化学的混乱が使用されました.

主要な成果:

  • ヒストンのアセチル化,クロマチンのリモデリング,RNAのスプライシング,およびシグナル伝達経路を含むPSDの中央および文脈依存のレギュレータを特定した.
  • 細胞サイクル遺伝子,特にDNA複製とG2相進行に関与する遺伝子の有意な増殖を発見した.
  • SとG2フェーズがPSDを弱めるのは,G1フェーズとは無関係なプラリポテンスの本質的な傾向による.

結論:

  • プラリポテンシー制御は細胞サイクル機構と密接に結びついています
  • 細胞サイクルのSとG2フェーズで活動する特定の経路は,多能状態の溶解を決定的に制限する.
  • これらの経路がG1段階に存在しないと,分化が開始される可能性があります.