JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us
このページは機械翻訳されています。他のページは英語で表示される場合があります。 View in English

TERTのクローン不活性化は,幹細胞の競争を阻害する

  • 0Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Nature +

|

2024年7月17日

|

2024年7月17日

PubMedで要約を見る

まとめ

この要約は機械生成です。

テロメラーゼ逆転写酵素 (TERT) は,その触媒機能とは独立して幹細胞の競争性を高めます. TERTは幹細胞の運命とMYCの腫瘍遺伝子の活動に影響を与え,クローン形成とゲノム調節に影響を与えます.

科学分野

  • 幹細胞生物学
  • 癌の研究
  • エピジェネティクス

背景

  • テロメラーゼ逆転写酵素 (TERT) を含むテロメラーゼは,テロメラー延長における役割により,幹細胞と癌に関連しています.
  • TERTの過剰発現は細胞増殖に影響するが,幹細胞機能における直接的な役割は不明である.
  • 幹細胞の競争は 組織ホメオスタシスの重要な要因です

研究 の 目的

  • 幹細胞の競争におけるTERTの役割を,その触媒活動とは独立に調査する.
  • TERTが幹細胞の適応と分化に影響を与えるメカニズムを探求する.
  • TERTと他の重要な調節遺伝子の間の潜在的な遺伝的リンクを明らかにする.

主な方法

  • マウスの精子幹細胞 (SSC) でTertの条件付消去.
  • TERT発現およびTERT不活性化SSCを追跡するための系統追跡.
  • クローン形成,幹細胞の分化,およびクロマチンのアクセシビリティの分析.
  • TERTで操作されたSSCにおけるMYC腫瘍遺伝子の活性に関する調査.

主要な成果

  • SSC の条件付きの Tert 削除は,競争力のあるクローン形成を著しく阻害しました.
  • TERTを発現するSSCは長生きのクローンを形成し,TERTの無活性化は分化を促進し,オープンクロマチンを減少させた.
  • 幹細胞の競争におけるTERTの役割は,その逆転写酵素活性とテロメラーゼ複合体とは独立していた.
  • TERTの不活性化により,MYCの腫瘍遺伝子の活性が低下し,MYCの過剰発現によって回復することができました.

結論

  • TERTは,その触媒活動から独立したメカニズムを通じて,幹細胞の競争を強化するために必要です.
  • 幹細胞の運命に影響を与えるTERTとMYC腫瘍遺伝子の間の遺伝的リンクが特定されました.
  • 高レベルのTERTは,幹細胞に選択的優位性を与え,雄の生殖系におけるテロメアの維持に寄与する.

関連する概念動画

Cancer Stem Cells and Tumor Maintenance 02:40

4.9K

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...

Multipotency of Hematopoietic Stem Cells 01:19

3.1K

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...

Loss of Tumor Suppressor Gene Functions 01:12

4.8K

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...

T Cell Activation and Clonal Selection 01:22

696

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

Replicative Cell Senescence 02:15

3.6K

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...

Stem Cell Niche 01:26

5.1K

The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...