ArticleThe Journal of experimental medicine2014
Improved HSC reconstitution and protection from inflammatory stress and chemotherapy in mice lacking granzyme B.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome.Nature communications · 2025Article
- Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation.Science China. Life sciences · 2025Article
- Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery.iScience · 2023Article
- Article
- CD244 expression represents functional decline of murine hematopoietic stem cells afteriScience · 2022Article
- Article
- Competitive sgRNA Screen Identifies p38 MAPK as a Druggable Target to Improve HSPC Engraftment.Cells · 2020Article
- Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation.Haematologica · 2019Article
- BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells.Haematologica · 2018Article
- Constitutive Activation of NIK Impairs the Self-Renewal of Hematopoietic Stem/Progenitor Cells and Induces Bone Marrow Failure.Stem cells (Dayton, Ohio) · 2017Article
- Regulation of stress-induced hematopoiesis.Current opinion in hematology · 2015Review
- Cutting the brakes on hematopoietic regeneration by blocking TGFβ to limit chemotherapy-induced myelosuppression.Molecular & cellular oncologyReview
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine protease granzyme B (GzmB) is stored in the granules of cytotoxic T and NK cells and facilitates immune-mediated destruction of virus-infected cells. In this study, we use genetic tools to report novel roles for GzmB as an important regulator of hematopoietic stem cell (HSC) function in response to stress. HSCs lacking the GzmB gene show improved bone marrow (BM) reconstitution associated with increased HSC proliferation and mitochondrial activity. In addition, recipients deficient in GzmB support superior engraftment of wild-type HSCs compared with hosts with normal BM niches. Stimulation of mice with lipopolysaccharide strongly induced GzmB protein expression in HSCs, which was mediated by the TLR4-TRIF-p65 NF-κB pathway. This is associated with increased cell death and GzmB secretion into the BM environment, suggesting an extracellular role of GzmB in modulating HSC niches. Moreover, treatment with the chemotherapeutic agent 5-fluorouracil (5-FU) also induces GzmB production in HSCs. In this situation GzmB is not secreted, but instead causes cell-autonomous apoptosis. Accordingly, GzmB-deficient mice are more resistant to serial 5-FU treatments. Collectively, these results identify GzmB as a negative regulator of HSC function that is induced by stress and chemotherapy in both HSCs and their niches. Blockade of GzmB production may help to improve hematopoiesis in various situations of BM stress.
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