ArticleMolecular endocrinology (Baltimore, Md.)2009
Pharmacological manipulation of the RAR/RXR signaling pathway maintains the repopulating capacity of hematopoietic stem cells in culture.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- NR2F6 regulates stem cell hematopoiesis and myelopoiesis in mice.Frontiers in immunology · 2024Article
- Article
- Ex Vivo Expansion and Homing of Human Cord Blood Hematopoietic Stem Cells.Advances in experimental medicine and biology · 2023Article
- Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage.Neuroscience bulletin · 2021Article
- Review
- Past, present, and future efforts to enhance the efficacy of cord blood hematopoietic cell transplantation.F1000Research · 2019Review
- Enhancing human cord blood hematopoietic stem cell engraftment by targeting nuclear hormone receptors.Current opinion in hematology · 2018Review
- MicroRNA expression profiling of intestinal mucosa tissue predicts multiple crucial regulatory molecules and signaling pathways for gut barrier dysfunction of AIDS patients.Molecular medicine reports · 2017Article
- Pathways of retinoid synthesis in mouse macrophages and bone marrow cells.Journal of leukocyte biology · 2016Article
- Retinoic acid regulates hematopoietic development from human pluripotent stem cells.Stem cell reports · 2015Article
- Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells.Mucosal immunology · 2013Article
- Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with radioprotective capacity.Stem cells (Dayton, Ohio) · 2010Article
- Minireview: Nuclear receptors, hematopoiesis, and stem cells.Molecular endocrinology (Baltimore, Md.) · 2010Review
- Nuclear receptor regulation of stemness and stem cell differentiation.Experimental & molecular medicine · 2009Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The retinoid X receptor (RXR) contributes to the regulation of diverse biological pathways via its role as a heterodimeric partner of several nuclear receptors. However, RXR has no established role in the regulation of hematopoietic stem cell (HSC) fate. In this study, we sought to determine whether direct modulation of RXR signaling could impact human HSC self-renewal or differentiation. Treatment of human CD34(+)CD38(-)lin(-) cells with LG1506, a selective RXR modulator, inhibited the differentiation of HSCs in culture and maintained long-term repopulating HSCs in culture that were otherwise lost in response to cytokine treatment. Further studies revealed that LG1506 had a distinct mechanism of action in that it facilitated the recruitment of corepressors to the retinoic acid receptor (RAR)/RXR complex at target gene promoters, suggesting that this molecule was functioning as an inverse agonist in the context of this heterodimer. Interestingly, using combinatorial peptide phage display, we identified unique surfaces presented on RXR when occupied by LG1506 and demonstrated that other modulators that exhibited these properties functioned similarly at both a mechanistic and biological level. These data indicate that the RAR/RXR heterodimer is a critical regulator of human HSC differentiation, and pharmacological modulation of RXR signaling prevents the loss of human HSCs that otherwise occurs in short-term culture.
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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.