somitic Wnt16/Notch経路は,血液形成幹細胞を特定する
Wilson K Clements1, Albert D Kim, Karen G Ong
1Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0380, USA.
Nature
|June 10, 2011
まとめ
Wnt16のシグナリングは,血液生成性幹細胞 (HSC) を特定するための新しいネットワークを制御します. この経路は,血液と免疫細胞の生成に不可欠であり,将来のHSC治療の可能性を秘めています.
科学分野:
- 発達生物学 発達生物学とは
- 幹細胞生物学 幹細胞生物学とは
- 分子遺伝学 分子遺伝学
背景:
- 血液形成性幹細胞 (HSC) は,生涯にわたる血液と免疫細胞の補充に不可欠です.
- HSCの臨床アプリケーションは,細胞数とドナーの互換性に関する課題に直面しています.
- 多能幹細胞からHSCを生成するには,胚の特異性を理解する必要があります.
研究 の 目的:
- 胚の発達中のHSC特異を制御する新しいメカニズムを解明する.
- HSCの早期形成に関与する重要な遺伝子調節体を特定する.
主な方法:
- 胚の発達を研究するためのモデル生物としてゼブラフィッシュを利用した.
- HSC仕様におけるWnt16シグナル伝達の役割を調査した.
- 分析された遺伝子発現パターンは,ノッチリガンド deltaC (dlc) と deltaD (dld) を含む.
主要な成果:
- Wnt16がHSCの特異化に不可欠な新しい遺伝ネットワークを制御することを実証しました.
- Wnt16の非正規のシグナル伝達が,ノッチリンガンド dlc と dld. のソミティック発現に必要であることを示した.
- Dlc と Dld の下流にある Notch シグナリングを,既知の細胞自律の Notch 要求に先立ち,決定的な血液形成に重要なものとして特定しました.
結論:
- Wnt16媒介のシグナリングは,HSCの仕様のための新しい経路を開始します.
- ソマイト特異的な遺伝子発現は,血性内皮の生成に不可欠である.
- 新しいノッチ依存リレー信号は,確立された経路と並行して早期のHSCを誘発する可能性が高い.
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関連する概念動画
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...
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...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:19Multipotency of Hematopoietic Stem Cells
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...
01:01Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...