Hematopoietic stem cell proliferative behavior as revealed by bromodeoxyuridine labeling

Area of Science:

• Hematology
• Stem Cell Biology
• Cellular Kinetics

Background:

• Hematopoietic stem cells (CFUS) are presumed to be a heterogeneous population.
• Variations in self-renewal and proliferation rates are suspected among CFUS.

Purpose of the Study:

• To characterize the hematopoietic stem cell (CFUS) population.
• To determine the proliferative activity and potential quiescence of CFUS.

Main Methods:

• Bromodeoxyuridine (BrdUrd) infusion in normal and hydroxyurea-pretreated mice.
• Assessment of BrdUrd-induced CFUS sensitization to ultraviolet light.
• Analysis of BrdUrd disappearance and sensitization decay curves.

Main Results:

• Identical exponential disappearance of BrdUrd sensitization with a T1/2 of six days was observed in both normal and regenerating CFUS pools.
• Absence of a secondary slope in the sensitization decay curve for recovered hydroxyurea-treated bone marrow.

Conclusions:

• Fewer than 10% of hematopoietic stem cells (CFUS) are likely mitotically quiescent for extended periods.
• The age structure of the CFUS population indicates a relatively short proliferative history for most cells.