Prolonged cell cycle transit is a defining and developmentally conserved hemopoietic stem cell property

Area of Science:

• Developmental biology
• Stem cell biology
• Hematopoiesis

Background:

• Adult hematopoietic stem cells (HSCs) are typically quiescent.
• HSCs can proliferate extensively when needed.
• Fetal liver HSCs extensively expand during development.

Purpose of the Study:

• To investigate the cell cycle kinetics of fetal liver HSCs during their expansion phase.
• To compare the cell cycle transit times of fetal HSCs with their progenitors.
• To understand the role of cell cycle duration in HSC maintenance and self-renewal.

Main Methods:

• Studied cell cycle kinetics of fetal liver HSCs.
• Performed competitive transplantation experiments.
• Analyzed cell cycle phases (G(0), G(1), S, G(2)-M) in HSCs and progenitors.
• Examined ex vivo expanded adult HSCs.

Main Results:

• Fetal liver HSCs have a prolonged average cell cycle transit time (10.6 h), twice that of progenitors.
• Fetal HSCs exhibit a prolonged G(1) phase and a period of relative quiescence (G(0)).
• Fetal HSCs are enriched in G(1) but also functional in S-G(2)-M, and adult HSCs also show prolonged cell cycle upon expansion.

Conclusions:

• A prolonged cell cycle, particularly in G(1), is a defining characteristic of stem cells.
• This extended cell cycle is likely critical for the maintenance and self-renewal of HSCs throughout development.
• HSCs are enriched in G(0)-G(1) phases regardless of developmental stage or condition, explaining their quiescent nature.