Related Experiment Video
Updated: May 27, 2026
08:00
Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Brad Dykstra1, Sandra Olthof, Jaring Schreuder
1Department of Cell Biology, European Research Institute on the Biology of Aging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. b.j.dykstra@med.umcg.nl
The Journal of Experimental Medicine
|November 24, 2011
Summary
Aging hematopoietic stem cells (HSCs) show both quantity and quality changes. Old HSCs have reduced self-renewal, homing, and proliferation, suggesting cellular aging impacts stem cell function.
Area of Science:
- Hematology
- Stem Cell Biology
- Gerontology
Background:
- Hematopoietic stem cell (HSC) populations change with aging.
- The causes of these changes (qualitative vs. quantitative alterations) are not fully understood.
Purpose of the Study:
- To investigate the quantitative and qualitative changes in the aging HSC compartment.
- To determine the functional impact of aging on HSC self-renewal, homing, and proliferation.
Main Methods:
- Clonal assays were used to assess HSC function.
- Long-term secondary transplantation assays measured self-renewal activity.
- Marrow-homing efficiency and seeding efficiency were evaluated.
- Co-culture assays with stromal cells assessed proliferative responses.
Main Results:
- Aging HSCs showed increased pool size with accumulation of myeloid-biased HSCs.
- Old HSCs exhibited reduced self-renewal, marrow-homing efficiency, and functional frequency.
- A twofold reduction in seeding efficiency and delayed proliferation were observed in old HSCs.
- Functional defects were characteristic of most old HSCs, not a specific subset.
Conclusions:
- The aging HSC compartment undergoes significant quantitative and qualitative alterations.
- Aging impairs HSC self-renewal, homing, and proliferative capacity.
- These functional deficits may arise from a process of cellular aging, as demonstrated by serial transplantation experiments.
Related Concept Videos
01:01Regulation 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...
01:19Multipotency 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...
01:21Hematopoiesis
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...