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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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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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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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Tissue Renewal without Stem Cells01:23

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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Stem cells are undifferentiated cells with extensive self-renewal properties that help them maintain their population during the fetal and adult stages of life. They can specialize in all cell types of the human body. However, their differential potential may vary and can be classified into five types. Stem cells can be (1) Totipotent, (2) Pluripotent, (3) Multipotent, (4) Oligopotent, and (5) Unipotent. Each stem cell has a specific origin; the fertilized egg or zygote is a totipotent cell and...
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Production of Formed Elements

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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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Simultaneous Assessment of Kinship, Division Number, and Phenotype via Flow Cytometry for Hematopoietic Stem and Progenitor Cells
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Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions.

Jeffrey M Bernitz1, Huen Suk Kim1, Ben MacArthur2

  • 1Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.

Cell
|November 15, 2016
PubMed
Summary

Hematopoietic stem cells (HSCs) remember their divisions, with long-term regenerative potential lost after four divisions. This cellular memory influences HSC aging and age-related changes.

Keywords:
agingcell division countingcellular memorydormancyhematopoietic stem cells

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Area of Science:

  • Cellular biology
  • Stem cell research
  • Aging research

Background:

  • Cell division counting is crucial for development, aging, and disease.
  • Hematopoietic stem cells (HSCs) are vital for blood cell production and maintaining tissue homeostasis.
  • Understanding HSC division history is key to comprehending aging and disease processes.

Purpose of the Study:

  • To track the cumulative division history of slow-cycling HSCs throughout adult life.
  • To investigate the role of cellular division counting and memory in HSC aging.
  • To determine the impact of division history on HSC regenerative potential and age-related changes.

Main Methods:

  • Tracking the cumulative divisional history of hematopoietic stem cells (HSCs) in vivo.
  • Analyzing HSC self-renewal divisions and entry into dormancy.
  • Assessing long-term regenerative potential after specific division counts.
  • Investigating age-related phenotypic changes in HSCs based on their division history.

Main Results:

  • A rare fraction of HSCs retains all long-term HSC (LT-HSC) activity.
  • HSCs undergo asynchronous, traceable symmetric self-renewal divisions (typically four) before dormancy.
  • Long-term regenerative potential is lost after the fifth division.
  • Age-related phenotypic changes in HSCs are dependent on their division history.

Conclusions:

  • HSCs accumulate discrete memory stages based on their division history.
  • Cellular memory plays a significant role in HSC aging.
  • The number of divisions dictates HSC regenerative potential and influences age-related alterations.