Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells
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Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.
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Comparison of gene expression profiles of HSCs, MuSCs, and HFSCs reveals a common gene signature in quiescent stem cells.
“a comparison of gene expression profiles of different types of quiescent stem cells, including HSCs45, MuSCs15 and HFSCs43, reveals a gene signature that is common to these quiescent stem cells (TABLE 1).”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [45]
Cyclin A2, cyclin B1, cyclin E2, and survivin are downregulated in quiescent HSCs, MuSCs, and HFSCs.
“Examples of genes that are downregulated in all three quiescent cell types (HSCs, MuSCs and HFSCs) include genes encoding cyclin A2, cyclin B1, cyclin E2 and survivin”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [45]
The common quiescent stem cell signature shows downregulation of genes involved in DNA replication and cell cycle progression.
“the signature reveals the downregulation of genes that are involved in DNA replication and cell cycle progression.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [45]
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Nakaoka, S., & Aihara, K. (2011) · Journal of Biological Dynamics · doi:10.1080/17513758.2011.588343 · Cited by 5 · see citing works
Syndecans in hematopoietic cells and their niches
Hagen, M. W., Setiawan, N. J., Woodruff, K. A., & Termini, C. M. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00326.2024 · Cited by 4 · see citing works
Resistance and DNA Repair Mechanisms of Cancer Stem Cells: Potential Molecular Targets for Therapy
Ahmad, A., Li, Y., Bao, B., & Sarkar, F. H. (2012) · Springer eBooks · doi:10.1007/978-94-007-4590-2_3 · Cited by 4 · see citing works
- Authors
- Forsberg, E. C., Passegué, E., Prohaska, S. S., Wagers, A. J., Koeva, M., Stuart, J. M., & Weissman, I. L.
- Affiliations
- University of California, Santa Cruz (US)
- Stanford Medicine (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Forsberg, E. Camilla
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-01-20
- Volume
- 5
- Issue
- 1
- Pages
- e8785
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2808351
- OpenAlex
- W2098528717
- Cited by
- 127
- References
- 88
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 11 · 2016: 12 · 2015: 16 · 2014: 7 · 2013: 13 · 2012: 10
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- National Science Foundation (0543197)
- Burroughs Wellcome Fund
- Alfred P. Sloan Foundation
- California Institute for Regenerative Medicine
- National Institutes of Health (5r01hl088582-05)
- National Heart, Lung, and Blood Institute (R01HL058770, 1R01HL088582-01, R01HL092471, R01-HL088582)
- National Cancer Institute (R01CA086065, R01CA086017)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK053074)
- Division of Biological Infrastructure
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem cells, HSC quiescence, hematopoietic stem cell mobilization, leukemia-initiating cells, chronic myeloid leukemia, gene expression profiling, bone marrow, cancer stem cells, stem cell self-renewal, HSC transplantation
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Disease Models, Animal, Flow Cytometry, Gene Expression Regulation, Hematopoietic Stem Cells, Mice, Inbred C57BL, Nucleic Acid Hybridization, Transcription, Genetic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Mice
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