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Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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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...
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Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

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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...
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Hematopoiesis01:21

Hematopoiesis

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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...
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Stem Cell Therapy for Tissue Regeneration01:21

Stem Cell Therapy for Tissue Regeneration

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Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
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Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

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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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Overview of Hematopoiesis01:20

Overview of Hematopoiesis

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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...
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A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
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アスコルバートは,血液形成幹細胞機能と白血病発生を調節する.

Michalis Agathocleous1, Corbin E Meacham1, Rebecca J Burgess1

  • 1Children's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Nature
|August 22, 2017
PubMed
まとめ
この要約は機械生成です。

メタボライトのレベルにおける生理学的変動は,幹細胞の機能を調節する. 血液形成幹細胞 (HSC) の高レベルのアスコルバートは,その頻度と機能を制限し,減少すると白血病が加速する.

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Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia
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11:56

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Modeling Chemotherapy Resistant Leukemia In Vitro
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科学分野:

  • 生物化学
  • 細胞生物学
  • 血液学

背景:

  • 幹細胞の運命は培養中の代謝産物によって影響を受けます.
  • 体内の生理学的代謝物による幹細胞機能の調節は不明である.

研究 の 目的:

  • 体内の幹細胞機能の調節における生理学的代謝物変異の役割を調査する.
  • 組織から直接稀な細胞集団を分析するためのメタボロミクス方法を開発する.

主な方法:

  • 希少細胞集団分析のための新しいメタボロミックスの方法を開発した.
  • ネズミの造血幹細胞 (HSC) と祖先細胞の代謝シグネチャーの比較
  • マウスのHSCに対する全身アスコルバートの減少の影響を調査した.

主要な成果:

  • 血液形成細胞の種類ごとに 異なった代謝シグネチャーが特定されました
  • HSCは高レベルのアスコルベットを示し,分化とともに減少した.
  • アスコルバートの枯渇は,部分的に腫瘍抑制剤Tet2を抑制することによって,HSCの頻度と機能を増加させた.
  • アスコルバートの枯渇はFlt3変異による白血病発生を加速し,食事によるアスコルバートの効果は逆転した.

結論:

  • HSCにおけるアスコルバートの蓄積は,Tet活性を促進し,HSCの頻度を制限し,白血病発生を抑制する.
  • アスコルバートは,Tet2依存および独立メカニズムを通じて,HSC機能と骨髄形成を否定的に調節する.
  • メタボライトのレベル,特にアスコルバートは,幹細胞機能を調節し,体内白血病を予防する上で重要な役割を果たします.