ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Cell-intrinsic in vivo requirement for the E47-p21 pathway in long-term hematopoietic stem cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia.Communications biology · 2022Article
- Inhibitor of DNA binding proteins revealed as orchestrators of steady state, stress and malignant hematopoiesis.Frontiers in immunology · 2022Review
- The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification.Frontiers in immunology · 2019Article
- Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4.Nature communications · 2018Article
- Bone Marrow-Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017Article
- Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura.Cephalalgia : an international journal of headache · 2017Article
- Article
- Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Requirement for ssbp2 in hematopoietic stem cell maintenance and stress response.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Hematopoiesis in steady-state versus stress: self-renewal, lineage fate choice, and the conversion of danger signals into cytokine signals in hematopoietic stem cells.Journal of immunology (Baltimore, Md. : 1950) · 2014Review
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Major regulators of long-term hematopoietic stem cell (LT-HSC) self-renewal and proliferation have been identified, but knowledge of their in vivo interaction in a linear pathway is lacking. In this study, we show a direct genetic link between the transcription factor E47 and the major cell cycle regulator p21 in controlling LT-HSC integrity in vivo under repopulation stress. Numerous studies have shown that E47 activates p21 transcription in hematopoietic subsets in vitro, and we now reveal the in vivo relevance of the E47-p21 pathway by reducing the gene dose of each factor individually (E47(het) or p21(het)) versus in tandem (E47(het)p21(het)). E47(het)p21(het) LT-HSCs and downstream short-term hematopoietic stem cells exhibit hyperproliferation and preferential susceptibility to mitotoxin compared to wild-type or single haploinsufficient controls. In serial adoptive transfers that rigorously challenge self-renewal, E47(het)p21(het) LT-HSCs dramatically and progressively decline, indicating the importance of cell-intrinsic E47-p21 in preserving LT-HSCs under stress. Transient numeric recovery of downstream short-term hematopoietic stem cells enabled the production of functionally competent myeloid but not lymphoid cells, as common lymphoid progenitors were decreased, and peripheral lymphocytes were virtually ablated. Thus, we demonstrate a developmental compartment-specific and lineage-specific requirement for the E47-p21 pathway in maintaining LT-HSCs, B cells, and T cells under hematopoietic repopulation stress in vivo.
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