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Related Concept Videos

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
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Related Experiment Video

Updated: Feb 24, 2026

A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
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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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Ascorbate regulates haematopoietic stem cell function and leukaemogenesis.

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
Summary
This summary is machine-generated.

Physiological variations in metabolite levels regulate stem-cell function. High ascorbate levels in hematopoietic stem cells (HSCs) limit their frequency and function, while depletion accelerates leukemia.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Hematology

Background:

  • Stem-cell fate is influenced by metabolites in culture.
  • Regulation of stem-cell function by physiological metabolite variations in vivo remains unclear.

Purpose of the Study:

  • To investigate the role of physiological metabolite variations in regulating stem-cell function in vivo.
  • To develop a metabolomics method for analyzing rare cell populations directly from tissues.

Main Methods:

  • Developed a novel metabolomics method for rare cell population analysis.
  • Compared metabolic signatures of mouse hematopoietic stem cells (HSCs) and progenitors.
  • Investigated the effects of systemic ascorbate depletion on HSCs in mice.

Main Results:

  • Distinct metabolic signatures were identified for each hematopoietic cell type.
  • HSCs exhibited high ascorbate levels, decreasing with differentiation.
  • Ascorbate depletion increased HSC frequency and function, partly by inhibiting the tumor suppressor Tet2.
  • Ascorbate depletion accelerated Flt3-mutated leukemogenesis, an effect reversed by dietary ascorbate.

Conclusions:

  • Ascorbate accumulation in HSCs promotes Tet activity, limiting HSC frequency and suppressing leukemogenesis.
  • Ascorbate negatively regulates HSC function and myelopoiesis via Tet2-dependent and independent mechanisms.
  • Metabolite levels, specifically ascorbate, play a crucial role in regulating stem-cell function and preventing leukemia in vivo.