Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification

Qiu, Jingyao; Nordling, Sofia; Vasavada, Hema; Butcher, Eugene C.; Hirschi, Karen K.

doi:10.1016/j.celrep.2020.108465

Cited by 12 publications

(3 citation statements)

References 47 publications

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“…Coronary artery development is impaired when cell cycle control is disrupted by overexpression of Nr2f2 to promote proliferation in the progenitor endothelial cells coming from the sinus venosus 3 . In addition, we previously found that p27-mediated cell cycle arrest is also required for endothelial cells to undergo hemogenic specification during definitive hematopoiesis 60 , and retinoic acid promotes early G1 arrest in human endothelial cells in vitro to enable hemogenic specification 61 . Thus, regulation of cell cycle state may be required to enable the phenotypic specialization of all endothelial cell subtypes.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell cycle state determines propensity for arterial-venous fate

et al. 2022

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During blood vessel development, endothelial cells become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, and removes metabolic waste from, all tissues. Arterial-venous specification occurs in conjunction with suppression of endothelial cell cycle progression; however, the mechanistic role of cell cycle state is unknown. Herein, using Cdh5-CreERT2;R26FUCCI2aR reporter mice, we find that venous endothelial cells are enriched for the FUCCI-Negative state (early G1) and BMP signaling, while arterial endothelial cells are enriched for the FUCCI-Red state (late G1) and TGF-β signaling. Furthermore, early G1 state is essential for BMP4-induced venous gene expression, whereas late G1 state is essential for TGF-β1-induced arterial gene expression. Pharmacologically induced cell cycle arrest prevents arterial-venous specification defects in mice with endothelial hyperproliferation. Collectively, our results show that distinct endothelial cell cycle states provide distinct windows of opportunity for the molecular induction of arterial vs. venous fate.

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Section: Discussionmentioning

confidence: 99%

Endothelial cell cycle state determines propensity for arterial-venous fate

et al. 2022

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“…Surprisingly, one study found that inhibiting RA led to modest increases in the expression of ASM markers (Chen et al, 2014). However, this previous work cultured explants in the presence of 10% serum, which can significantly alter the concentration of retinol (Engedal et al, 2006) and would also be expected to alter cell proliferation, which can affect RA responsiveness in some tissues (Marcelo et al, 2013;Qiu et al, 2020). Here, we measured the distribution of αSMA protein, which forms the core of the smooth muscle cytoskeletal machinery (Jaslove and Nelson, 2018), and found that inhibiting RA decreases αSMA-positive cells at the tips of epithelial branches.…”

Section: Discussionmentioning

confidence: 94%

Transmural pressure signals through retinoic acid to regulate lung branching

et al. 2022

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During development, the mammalian lung undergoes several rounds of branching, the rate of which is tuned by the relative pressure of the fluid within the lumen of the lung. We carried out bioinformatics analysis of RNA-sequencing of embryonic mouse lungs cultured under physiologic or sub-physiologic transmural pressure and identified transcription factor-binding motifs near genes whose expression changes in response to pressure. Surprisingly, we found retinoic acid (RA) receptor binding sites significantly overrepresented in the promoters and enhancers of pressure-responsive genes. Consistently, increasing transmural pressure activates RA signaling, and pharmacologically inhibiting RA signaling decreases airway epithelial branching and smooth muscle wrapping. We found that pressure activates RA signaling through the mechanosensor Yap. A computational model predicts that mechanical signaling through Yap and RA affects lung branching by altering the balance between epithelial proliferation and smooth muscle wrapping, which we test experimentally. Our results reveal that transmural pressure signals through RA to balance the relative rates of epithelial growth and smooth muscle differentiation in the developing mouse lung and identify RA as a previously unreported component in the mechanotransduction machinery of embryonic tissues.

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“…With regards to cellular proliferation and differentiation, ATRA exerts its influence by promoting the progression of cells through the cell cycle, particularly the G1 phase. This is achieved through the activation of genes supportive of cell division while concurrently suppressing genes associated with cell cycle arrest [131]. Moreover, ATRA signaling contributes significantly to morphogenesis.…”

Section: Growth Cellular Differentiation Morphogenesis and Reproducti...mentioning

confidence: 99%

Pet Wellness and Vitamin A: A Narrative Overview

Shastak,

Pelletier

2024

Animals

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The health of companion animals, particularly dogs and cats, is significantly influenced by nutrition, with vitamins playing a crucial role. Vitamin A, in particular, is indispensable, with diverse roles ranging from vision to immune modulation and reproduction. Despite its importance, the metabolism and dietary requirements of vitamin A in companion animals remain complex and not fully understood. This review provides a comprehensive overview of the historical perspective, the digestion, the metabolism, the physiological roles, the deficiency, the excess, and the interactions with other micronutrients of vitamin A in companion animals. Additionally, it highlights future research directions and gaps in our understanding. Insights into the metabolism of vitamin A in companion animals, personalized nutrition strategies based on genetic variability, longitudinal studies tracking the status of vitamin A, and investigations into its immunomodulatory effects are crucial for optimizing pet health and wellness. Furthermore, understanding the stability and bioavailability of vitamin A in pet food formulations is essential for ensuring the provision of adequate micronutrients. Overall, this review underscores the importance of vitamin A in companion animal nutrition and the need for further research to enhance our understanding and to optimize dietary recommendations for pet health and well-being.

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Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification

Cited by 12 publications

References 47 publications

Endothelial cell cycle state determines propensity for arterial-venous fate

Endothelial cell cycle state determines propensity for arterial-venous fate

Transmural pressure signals through retinoic acid to regulate lung branching

Pet Wellness and Vitamin A: A Narrative Overview

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