ArticleBMC biology2009
Retinoic acid enhances skeletal muscle progenitor formation and bypasses inhibition by bone morphogenetic protein 4 but not dominant negative beta-catenin.
Article in BMC biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03632876 (Vitamin A in Sickle Cell Disease), which is not on this map. Cited by 46 papers.
What it found
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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.
The trial behind it
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.
Vitamin A in Sickle Cell Disease: Improving Sub-optimal Status With Supplementation
Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
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- Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer.Journal of stem cell research & therapy · 2023Article
- Controlling neural territory patterning from pluripotency using a systems developmental biology approach.iScience · 2022Article
- Production of Innervated Skeletal Muscle Fibers Using Human Induced Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
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- Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling.Frontiers in cell and developmental biology · 2021Article
- MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia.Frontiers in oncology · 2020Review
- Skeletal Muscle Regenerative Engineering.Regenerative engineering and translational medicine · 2019Article
- Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro.Experimental cell research · 2017Article
- Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage.Cell & bioscience · 2017Review
- Repression of GPRC5A is associated with activated STAT3, which contributes to tumor progression of head and neck squamous cell carcinoma.Cancer cell international · 2017Article
- BRG1 interacts with GLI2 and binds Mef2c gene in a hedgehog signalling dependent manner during in vitro cardiomyogenesis.BMC developmental biology · 2016Article
- Myogenic Differentiation of Mouse Embryonic Stem Cells That Lack a Functional Pax7 Gene.Stem cells and development · 2016Article
- Implication of retinoic acid receptor selective signaling in myogenic differentiation.Scientific reports · 2016Article
- From pluripotency to myogenesis: a multistep process in the dish.Journal of muscle research and cell motility · 2015Review
- Identification of embryonic stem cell activities in an embryonic cell line derived from marine medaka (Oryzias dancena).Fish physiology and biochemistry · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundUnderstanding stem cell differentiation is essential for the future design of cell therapies. While retinoic acid (RA) is the most potent small molecule enhancer of skeletal myogenesis in stem cells, the stage and mechanism of its function has not yet been elucidated. Further, the intersection of RA with other signalling pathways that stimulate or inhibit myogenesis (such as Wnt and BMP4, respectively) is unknown. Thus, the purpose of this study is to examine the molecular mechanisms by which RA enhances skeletal myogenesis and interacts with Wnt and BMP4 signalling during P19 or mouse embryonic stem (ES) cell differentiation.
resultsTreatment of P19 or mouse ES cells with low levels of RA led to an enhancement of skeletal myogenesis by upregulating the expression of the mesodermal marker, Wnt3a, the skeletal muscle progenitor factors Pax3 and Meox1, and the myogenic regulatory factors (MRFs) MyoD and myogenin. By chromatin immunoprecipitation, RA receptors (RARs) bound directly to regulatory regions in the Wnt3a, Pax3, and Meox1 genes and RA activated a beta-catenin-responsive promoter in aggregated P19 cells. In the presence of a dominant negative beta-catenin/engrailed repressor fusion protein, RA could not bypass the inhibition of skeletal myogenesis nor upregulate Meox1 or MyoD. Thus, RA functions both upstream and downstream of Wnt signalling. In contrast, it functions downstream of BMP4, as it abrogates BMP4 inhibition of myogenesis and Meox1, Pax3, and MyoD expression. Furthermore, RA downregulated BMP4 expression and upregulated the BMP4 inhibitor, Tob1. Finally, RA inhibited cardiomyogenesis but not in the presence of BMP4.
conclusionRA can enhance skeletal myogenesis in stem cells at the muscle specification/progenitor stage by activating RARs bound directly to mesoderm and skeletal muscle progenitor genes, activating beta-catenin function and inhibiting bone morphogenetic protein (BMP) signalling. Thus, a signalling pathway can function at multiple levels to positively regulate a developmental program and can function by abrogating inhibitory pathways. Finally, since RA enhances skeletal muscle progenitor formation, it will be a valuable tool for designing future stem cell therapies.
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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.