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Updated: Jul 1, 2025
07:14
A Culture Method to Maintain Quiescent Human Hematopoietic Stem Cells
Published on: May 17, 2021
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The Essence of Quiescence
Peter Quesenberry1, Mark Dooner1, Mandy Pereira1
1Department of Medicine, Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, Rhode Island, USA.
Stem Cells and Development
|March 6, 2024
Summary
Hematopoietic stem cells (HSCs) are not predominantly dormant; a significant portion actively cycles. This challenges long-held beliefs and reveals actively cycling stem cells within lineage-positive cells.
Area of Science:
- Hematology
- Stem Cell Biology
- Cell Cycle Regulation
Background:
- Hematopoietic stem cells (HSCs) were historically considered largely quiescent.
- This paradigm has influenced decades of stem cell research and therapeutic strategies.
- A potential heuristic error in understanding HSC dormancy has persisted.
Purpose of the Study:
- To challenge the prevailing notion of HSC dormancy.
- To investigate the cell cycle status of functional, engraftable HSCs.
- To re-evaluate the role of lineage-positive cells in hematopoiesis.
Main Methods:
- Analysis of HSC cell cycle status in whole unseparated bone marrow.
- Application of tritiated thymidine suicide assays.
- Utilizing bromodeoxyuridine labeling assays in murine models.
- Examination of both whole bone marrow and purified lineage-negative HSCs.
Main Results:
- A significant proportion of engraftable HSCs are actively cycling, not quiescent.
- Actively cycling HSCs were identified within the lineage-positive cell fraction.
- Findings were confirmed across multiple experimental assays and models.
Conclusions:
- Hematopoietic stem cells are characterized by active cycling and expression of differentiation epitopes.
- This corrects a fundamental error in stem cell biology.
- Provides new insights into the behavior and regulation of actively cycling HSCs.
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