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Related Concept Videos

Regulation of Hematopoietic Stem Cells01:01

Regulation 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...
Multipotency of Hematopoietic Stem Cells01:19

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 Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
Differentiation of Common Myeloid Progenitor Cells01:15

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...
Hematopoiesis01:21

Hematopoiesis

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...
Production of Formed Elements01:34

Production of Formed Elements

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...

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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
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Methylation damage response in hematopoietic progenitor cells.

Ida Casorelli1, Elvira Pelosi, Mauro Biffoni

  • 1Section of Experimental Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.

DNA Repair
|May 18, 2007
PubMed
Summary

Hematopoietic stem cells (CD34+) show higher DNA repair gene expression than mature cells (CD34-). Both cell types are equally sensitive to methylation damage when actively cycling.

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Area of Science:

  • Molecular Biology
  • Hematology
  • DNA Repair Mechanisms

Background:

  • Multipotent CD34(+) hematopoietic stem cells and mature CD34(-) cells differ in their cellular functions and responses.
  • DNA damage response pathways are crucial for maintaining genomic integrity, particularly in stem cells.

Purpose of the Study:

  • To compare the cellular response to methylation DNA damage between CD34(+) stem cells and CD34(-) mature cells.
  • To investigate the role of DNA repair gene expression in differential sensitivity to DNA damage.

Main Methods:

  • Isolation of CD34(+) and CD34(-) cells from cord blood.
  • Cytofluorimetric analysis to assess cell cycle phase.
  • Quantitative RT-PCR to measure DNA repair gene expression.
  • Treatment with N-methyl-N-nitrosourea (MNU) and MGMT inhibitor O(6)-benzylguanine.

Main Results:

  • Freshly isolated CD34(+) cells exhibited higher expression of DNA repair genes (MMR, BER, MGMT) compared to CD34(-) cells.
  • Expanded CD34(+) and CD34(-) cells, both cycling, showed similar sensitivity to MNU-induced apoptosis.
  • MGMT inhibition increased MNU cytotoxicity, confirming its protective role.

Conclusions:

  • Cycling CD34(+) and CD34(-) cells possess similar sensitivity to methylation DNA damage.
  • Differential expression of DNA repair genes in non-cycling cells may contribute to stem cell resilience.
  • MGMT and mismatch repair (MMR) pathways are critical in mitigating methylation-induced DNA damage.