骨髄原菌群の形成は緊急および白血病骨髄形成を促す
Aurélie Hérault1, Mikhail Binnewies1, Stephanie Leong1
1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, California 94143, USA.
Nature
|March 30, 2017
まとめ
骨髄の再生と白血病の間,粒細胞/マクロファージ先駆体 (GMP) は動的クラスターを形成する. これらのクラスターはニッチ信号と 自己再生ネットワークによって制御され 血液生成と病気に関する 新たな洞察を明らかにします
科学分野:
- 血液学
- 細胞生物学
- 発達生物学
背景:
- 骨髄における骨髄分化の空間的組織はよく理解されていません.
- グラヌロサイト/マクロファージ (GMP) は,血液生成における重要な細胞である.
研究 の 目的:
- 安定状態,緊急状態,および白血病性骨髄形成中のGMPの局所的行動と空間的組織を調査する.
- GMPの行動と差別化を制御する規制メカニズムを特定する.
主な方法:
- マウスモデルにおけるGMP行動を追跡するインビボ画像技術.
- 骨髄のニッチ信号と遺伝子発現ネットワークの分析
主要な成果:
- 安定状態では,GMPは散らばっており,再生過程では,局所的に分化するダイナミックなクラスターを形成します.
- 再生するGMPクラスタの形成は,特定の骨髄のニッチ信号と祖先の自己再生ネットワーク (Irf8とβ-カテニン) によって制御されます.
- 白血病では,持続的な自己更新活性化と抑制信号の欠如により,GMPクラスターが持続的に生成されます.
結論:
- GMPは,緊急骨格形成の制御に不可欠な,現場でダイナミックなクラスタリング行動を示す.
- このGMPのクラスタリングメカニズムは 白血病で異常な形でハイジャックされ,制御不能な増殖につながります.
- この研究は骨髄における 骨髄分化の新しい時空的組織を発見した.
関連する概念動画
01:15Differentiation of Common Myeloid Progenitor Cells
4.1K
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...
4.1K
01:34Production of Formed Elements
5.1K
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...
5.1K
01:21Lineage Commitment
4.5K
Commitment is the process whereby stem cells:
4.5K
01:21Hematopoiesis
9.5K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
9.5K
01:20Overview of Hematopoiesis
10.6K
Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
10.6K
01:19Multipotency of Hematopoietic Stem Cells
4.0K
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...
4.0K