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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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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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Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

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Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
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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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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Production of Formed Elements01:34

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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.
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Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells
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CD11a regulates hematopoietic stem and progenitor cells.

Lifei Hou1,2,3,4, Koichi Yuki1,2,3,4

  • 1Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA, United States.

Frontiers in Immunology
|October 2, 2023
PubMed
Summary

Integrin alphaLbeta2 (CD11a) deficiency boosts hematopoietic stem and progenitor cell (HSPC) activity and proliferation. This effect is mediated by increased IL-27 cytokine production, not cell-intrinsic mechanisms.

Keywords:
CD11ahematopoietic stem and progenitor cells (HPSCs)il-27inflammationsepsis

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Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • Integrin alphaLbeta2 (CD11a/CD18, CD11a) is a key molecule in leukocyte adhesion and immune responses.
  • Its specific function within the bone marrow microenvironment remains underexplored.

Purpose of the Study:

  • To investigate the role of CD11a in hematopoietic stem and progenitor cells (HPSCs) within the bone marrow.
  • To elucidate the mechanisms underlying CD11a's influence on HSPC activity.

Main Methods:

  • Expression analysis of CD11a on various HPSC subsets.
  • Assessment of HPSC activity and proliferation following CD11a deficiency under lipopolysaccharide (LPS) stimulation.
  • Mixed chimera experiments to evaluate cell-intrinsic versus extrinsic effects.
  • Quantification of cytokine production, including IL-27, in vivo and in vitro.

Main Results:

  • CD11a is expressed across all HPSC subsets.
  • CD11a deficiency leads to enhanced HPSC counts and proliferation, particularly under LPS stimulation.
  • Mixed chimera experiments indicate the observed phenotype is not cell-intrinsic.
  • Significantly upregulated production of IL-27, a known HSPC proliferation driver, was observed in CD11a-deficient contexts.

Conclusions:

  • CD11a plays a regulatory role in HPSC activity within the bone marrow.
  • The absence of CD11a enhances HSPC proliferation indirectly through increased IL-27 production.
  • This study reveals a novel biological function for CD11a involving cytokine regulation in hematopoiesis.