Inflammation: a key regulator of hematopoietic stem cell fate in health and disease
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Hematopoietic stem cells (HSCs) are responsible for lifelong production of blood cells. At the same time, they must respond rapidly to acute needs such as infection or injury. Significant interest has emerged in how inflammation regulates HSC fate and how it affects the long-term functionality of HSCs and the blood system as a whole. Here we detail recent advances and unanswered questions at the intersection between inflammation and HSC biology in the contexts of development, aging, and hematological malignancy.
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Chronic inflammation, often associated with increased IL-1 activity, is a common phenotype in individuals at risk for hematological malignancy, which can be related to several preexisting factors, including aging/tissue decline, genotoxin exposure, metabolic dysfunction, and/or autoimmune disease.
“Chronic inflammation, often associated with increased IL-1 activity, is a common phenotype in individuals at risk for hematological malignancy, which can be related to several preexisting factors, including aging/tissue decline, genotoxin exposure, metabolic dysfunction, and/or autoimmune disease (Barreyro et al., 2018; Pietras, 2017).”
From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Pietras, 2017
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Experimental — accuracy not yet measuredDysregulated inflammatory signaling has emerged as a key partner alongside oncogenic mutations in the development and/or progression of hematological malignancy.
“Dysregulated inflammatory signaling has emerged as a key partner alongside oncogenic mutations in the development and/or progression of hematological malignancy (Barreyro et al., 2018; Pietras, 2017).”
From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Pietras, 2017
Quiescence prevents HSC depletion during chronic inflammation, indicating that multipotent progenitor (MPP) cells compensate the ongoing need, minimizing the necessity for HSCs to proliferate.
“Quiescence prevents HSC depletion during chronic inflammation.This indicates that multipotent progenitor (MPP) cells, responsible for daily blood maintenance, compensate the ongoing need, thereby minimizing the necessity for HSCs to proliferate.25”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [25]
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Clonal hematopoiesis: Mutation-specific adaptation to environmental change
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“While transient proliferative responses to stress are crucial adaptations that promote organismal survival, long-term loss of HSC quiescence can lead to bone marrow failure, overproduction of potentially toxic cell types and/or hematological malignancy (Pietras, 2017).”
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Self-citationRabe, J. L., Hernandez, G., Chavez, J. S., Mills, T. S., Nerlov, C., & Pietras, E. M. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2019.12.003 · Cited by 49 · see citing works
Self-citationPI3K alpha and delta promote hematopoietic stem cell activation
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PU.1 is required to restrain myelopoiesis during chronic inflammatory stress
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“IL-1β is produced in response to a wide range of physiological insults, and IL-1 signaling is closely linked to a wide variety of chronic inflammatory diseases, where it plays a critical role in the activation of inflammatory myelopoiesis (Ueda et al., 2009; Dinarello, 2011; Mirantes et al., 2014; Pietras, 2017).”
BackgroundSelf-citation
- Authors
- Pietras, E. M.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Pietras, Eric M.
- ORCID
- Pietras, Eric M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2017-10-12
- Volume
- 130
- Issue
- 15
- Pages
- 1693-1698
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC5639485
- OpenAlex
- W2751980430
- Cited by
- 417
- References
- 92
- Citations by year
- 2026: 43 · 2025: 46 · 2024: 49 · 2023: 43 · 2022: 50 · 2021: 76 · 2020: 48 · 2019: 38 · 2018: 24
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boettcher Foundation
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK098315)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, inflammation, HSC quiescence, HSC aging, hematopoiesis, hematologic malignancies
- MeSH terms
- Aging, Animals, Disease, Health, Hematopoietic Stem Cells, Humans, Inflammation, Cell Lineage
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