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Related Concept Videos

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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Using mitochondrial activity to select for potent human hematopoietic stem cells.

Jiajing Qiu1, Jana Gjini1,2, Tasleem Arif1

  • 1Department of Cell, Developmental & Regenerative Biology.

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|March 12, 2021
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Identifying potent hematopoietic stem cells (HSCs) is key for transplantation. Researchers found that HSCs with lower mitochondrial activity, indicated by mitochondrial membrane potential (MMP), are more potent and better for long-term engraftment.

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Area of Science:

  • Cell Biology
  • Hematology
  • Stem Cell Biology

Background:

  • Hematopoietic cell transplantation is crucial for treating blood disorders.
  • Challenges exist in obtaining sufficient potent hematopoietic stem cells (HSCs) for long-term engraftment due to metabolic limitations.
  • Mitochondrial function is implicated in HSC potency and behavior.

Purpose of the Study:

  • To investigate the heterogeneity of mitochondrial activity within purified human HSCs.
  • To determine the correlation between mitochondrial activity and HSC potency.
  • To identify a method for isolating highly potent HSCs for clinical applications.

Main Methods:

  • Purification of human CD34+CD38-CD45RA-CD90+CD49f+ HSCs.
  • Assessment of mitochondrial membrane potential (MMP) to measure mitochondrial activity.
  • In vitro long-term culture initiating cell assays.
  • In vivo transplantation studies in immunodeficient mice.

Main Results:

  • Human HSCs exhibit heterogeneous mitochondrial activity (MMP).
  • HSCs with the lowest MMP (MMP-low) demonstrated significantly higher potency and long-term repopulating capacity in vivo compared to MMP-high HSCs.
  • MMP-low HSCs showed fragmented mitochondria and a delayed cell-cycle priming profile, suggesting quiescence.

Conclusions:

  • Lowest MMP identifies highly potent, likely dormant, human HSCs within purified populations.
  • Mitochondrial activity and morphology are critical intrinsic regulators of HSC quiescence and potency.
  • This finding offers a novel strategy for isolating superior HSCs for hematopoietic cell transplantation.