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Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation
Published on: November 10, 2017
A non-redundant function of cyclin E1 in hematopoietic stem cells
Stefano Campaner1, Andrea Viale, Serena De Fazio
1Center for Genomic Science of IIT@SEMM; Istituto Italiano di Tecnologia (IIT); Milan, Italy.
Cell Cycle (Georgetown, Tex.)
|October 5, 2013
Summary
Cyclin E1, not E2, is vital for hematopoietic stem cell (HSC) function, controlling their exit from quiescence. Its absence impairs HSCs under stress but may protect them during aging and transplantation.
Area of Science:
- Hematology
- Stem Cell Biology
- Cell Cycle Regulation
Background:
- Hematopoietic stem cells (HSCs) require a balance between quiescence and proliferation for lifelong function.
- Cyclins E1 and E2 regulate quiescence exit in fibroblasts, but their role in HSCs is not well understood.
Purpose of the Study:
- To investigate the role of Cyclin E1 and E2 in mouse hematopoietic stem cell function.
- To determine the impact of Cyclin E1 loss on HSCs under homeostatic and stress conditions.
Main Methods:
- Long-term culture-initiating cell (LTC-IC) assays to assess progenitor activity.
- In vivo studies using Ccne1(-/-) mice under homeostatic and 5-fluorouracil (5-FU) induced stress conditions.
- Bone marrow serial transplantation assays to evaluate HSC competitive potential.
Main Results:
- Loss of Cyclin E1 (Ccne1), but not E2, impaired primitive hematopoietic progenitor colony formation.
- Ccne1(-/-) mice exhibited normal hematopoiesis under homeostatic conditions but severe impairment after 5-FU treatment.
- Ccne1(-/-) HSCs showed reduced cell cycle entry post-stress, leading to decreased hematopoiesis and survival.
- Cyclin E1 deficiency increased HSC quiescence in aged mice and conferred a competitive advantage in transplantation.
Conclusions:
- Cyclin E1 plays a non-redundant role in controlling HSC exit from quiescence.
- The function of Cyclin E1 in HSCs is context-dependent, influencing hematopoiesis maintenance under stress, aging, and transplantation scenarios.
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