プロスタグランジンE2によるディフェンシャル幹細胞とプロジェント細胞の密輸.
Jonathan Hoggatt1, Khalid S Mohammad, Pratibha Singh
1Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Nature
|March 15, 2013
まとめ
非ステロイド性抗炎症薬 (NSAIDs) は,プロスタグランジンE2 (PGE2) シグナル伝達を阻害することによって,骨髄のニッチから血球形成性幹細胞 (HSC) の脱出を促進します. これは,HSCの移植を強化し,移植のための治療戦略を提供します.
科学分野:
- 血液学 ヘマトロジ
- 幹細胞生物学 幹細胞生物学
- 免疫学 免疫学とは
背景:
- 造血幹細胞 (HSC) は,生涯にわたる血液生産のためにニッチの規制を必要とします.
- プロスタグランディンE2 (PGE2) は,HSC機能において,既知のex vivo役割を持っています.
- 骨髄のニッチ内のHSCのインビボの調節は完全に理解されていません.
研究 の 目的:
- 骨髄のニッチ内の血球形成性幹細胞 (HSC) 行動の調節における内生性前列腺素E2 (PGE2) の役割を調査する.
- 非ステロイド性抗炎症薬 (NSAID) 治療がHSCの動員と移植に影響するかどうかを判断する.
- NSAID媒介のHSC動員による治療の可能性を調査する.
主な方法:
- ネズミのNSAID治療は,内在的なPGE2.2を抑制するために行われます.
- 骨髄と外周血液からのHSC出血の分析.
- 幹細胞と親細胞の動員メカニズムの評価.
- 血液形成移植の再生能力と長期的な移植の評価.
- 非ヒトの霊長類と人間のボランティアにおけるNSAID治療.
- PGE2受容体 (EP4) ノックアウトマウス研究.
主要な成果:
- NSAID治療は,SDF-1-CXCR4軸から独立して,骨髄から控えめなHSCの脱出を誘導しました.
- HSCの脱出は,ニッチの衰弱とオステオポントン濃度の低下と関連していました.
- NSAIDで動員された血液形成移植は,優れた再生能力と移植を示しました.
- NSAID媒介による脱出は,ヒトを含む種間で確認されました.
- 減少したE-プロスタノイド4 (EP4) 受容体のシグナル伝達により,先駆体膨張が低下し,幹/先駆体脱出が促進された.
結論:
- 内生PGE2は,EP4受容体を通して信号を送り,骨髄のニッチ内でHSCを保持する上で重要な役割を果たします.
- NSAID治療は,強化された治療的移植のためにHSCを動員する実行可能な戦略です.
- この研究は,HSCの保持と動員のための新しい規制メカニズムを明らかにしています.
関連する概念動画
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
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.
Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
Cell Migration
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cell Migration
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
Multipotency 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...
Lineage Commitment
Commitment is the process whereby stem cells:


