ArticleProceedings of the National Academy of Sciences of the United States of America2007
HOXB4's road map to stem cell expansion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 89 citations in OpenAlex.
- HOXB4/METTL7B cascade mediates malignant phenotypes of hepatocellular carcinoma through TKT m6A modification.Biology direct · 2025Article
- ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3.BMC medical genomics · 2024Article
- Characterization of Expression-Based Gene Clusters Gives Insights into Variation in Patient Response to Cancer Therapies.Cancer informatics · 2024Article
- HOX Protein Activity Regulation by Cellular Localization.Journal of developmental biology · 2021Review
- Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators.Current genomics · 2019Review
- Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors.Stem cell research & therapy · 2019Article
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- HOXB4 Promotes Hemogenic Endothelium Formation without Perturbing Endothelial Cell Development.Stem cell reports · 2018Article
- HOXB4 IncreasesTransfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2017Article
- Conditional Loss ofFrontiers in molecular neuroscience · 2017Article
- TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis.In vitro cellular & developmental biology. Animal · 2016Article
- HOXA4 provides stronger engraftment potential to short-term repopulating cells than HOXB4.Stem cells and development · 2015Article
- Gene-based association analysis identified novel genes associated with bone mineral density.PloS one · 2015Article
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- Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.Scientific reports · 2013Article
- USF1 and hSET1A mediated epigenetic modifications regulate lineage differentiation and HoxB4 transcription.PLoS genetics · 2013Article
- Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein.PloS one · 2013Article
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- Serum- and stromal cell-free hypoxic generation of embryonic stem cell-derived hematopoietic cells in vitro, capable of multilineage repopulation of immunocompetent mice.Stem cells translational medicine · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeodomain-containing transcription factors are important regulators of stem cell behavior. HOXB4 mediates expansion of adult and embryo-derived hematopoietic stem cells (HSCs) when expressed ectopically. To define the underlying molecular mechanisms, we performed gene expression profiling in combination with subsequent functional analysis with enriched adult HSCs and embryonic derivatives expressing inducible HOXB4. Thereby, we identified a set of overlapping genes that likely represent "universal" targets of HOXB4. A substantial number of loci are involved in signaling pathways important for controlling self-renewal, maintenance, and differentiation of stem cells. Functional assays performed on selected pathways confirmed the biological coherence of the array results. HOXB4 activity protected adult HSCs from the detrimental effects mediated by the proinflammatory cytokine TNF-alpha. This protection likely contributes to the competitive repopulation advantage of HOXB4-expressing HSCs observed in vivo. The concept of TNF-alpha inhibition may also prove beneficial for patients undergoing bone marrow transplantation. Furthermore, we demonstrate that HOXB4 activity and FGF signaling are intertwined. HOXB4-mediated expansion of adult and ES cell-derived HSCs was enhanced by specific and complete inhibition of FGF receptors. In contrast, the expanding activity of HOXB4 on hematopoietic progenitors in day 4-6 embryoid bodies was blunted in the presence of basic FGF (FGF2), indicating a dominant negative effect of FGF signaling on the earliest hematopoietic cells. In summary, our results strongly suggest that HOXB4 modulates the response of HSCs to multiple extrinsic signals in a concerted manner, thereby shifting the balance toward stem cell self-renewal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.