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関連する概念動画

Renewal of Intestinal Stem Cells01:23

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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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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...
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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...
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腸内密室における代謝同一性の相互作用は,幹細胞の機能をサポートする.

Maria J Rodríguez-Colman1, Matthias Schewe2, Maaike Meerlo1

  • 1Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584CG Utrecht, The Netherlands.

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|March 9, 2017
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まとめ

代謝は腸の幹細胞の再生を促します パネス細胞はLgr5+幹細胞に乳酸を供給し,反応性酸素種のシグナル伝達によってミトコンドリアの機能と分化をサポートする.

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科学分野:

  • 胃腸内科
  • 細胞生物学
  • メタボリズム

背景:

  • 小腸の表皮は,暗号の基礎にあるLgr5+幹細胞によって,急速な自己再生をします.
  • 幹細胞機能を調節するシグナル伝達経路は知られているが,上皮の恒常性への代謝の貢献はほとんど未知のままである.

研究 の 目的:

  • 腸の幹細胞とパネス細胞の 異なる代謝プログラムを調査する
  • 腸内皮質ホメオスタシスと幹細胞機能の維持における細胞代謝の役割を明らかにする.

主な方法:

  • マウスの小腸からLgr5+CBCとパネス細胞を分離した.
  • ミトコンドリアの活性と糖分解の評価
  • ミトコンドリアの活性と糖分解の抑制
  • オルガノイド形成測定法
  • 反応性酸素種のシグナル伝達とp38 MAPK活性化の分析

主要な成果:

  • Lgr5+ CBCは,パネス細胞と比較して,より高いミトコンドリア活性を示します.
  • Lgr5+ CBCにおけるミトコンドリア活性抑制は幹細胞機能を損なう.
  • パネス細胞の糖分分解の抑制は幹細胞機能にも影響を及ぼします.
  • パネス細胞はLgr5+CBCに乳酸を供給し,酸化性リン酸化をサポートする.
  • 酸化性リン酸化は,ROSシグナル伝達を通じてp38 MAPKを活性化し,暗号の成熟を促進する.

結論:

  • Lgr5+ CBCとパネス細胞の異なる代謝プログラムは,腸の幹細胞機能にとって極めて重要です.
  • パネス細胞由来乳酸は,Lgr5+ CBCの代謝と分化をサポートする.
  • ミトコンドリアの酸化リン酸化とROSシグナリングは,腸内密室の細胞分化の主な原動力である.