Project description:Embryonic stem cells (ESC) are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass in their developmental potential. ESCs pluripotency is maintained through a complex interplay of different signaling pathways and a network of transcription factors, which is centered around Oct3/4, Sox2 and Nanog. Although, in general, much is known about this pluripotency self-renewal circuitry, the molecular events that lead ESC to exit from pluripotency and begin differentiation are currently less known. Retinoic acid, an active metabolite of the vitamin A (retinol), plays important and pleiotropic roles in vertebrate embryonic development and ESC differentiation. Here we demonstrate that RA promotes early steps of ESC differentiation, and that ESC increase their capacity to synthesize RA during spontaneous differentiation as embryoid bodies, up-regulating the RA biosynthetic pathway components RDH1, RDH10, ADH3, RALDH2, and CRABP2. Microarray derived from total RNA of mESC not treated or treated with all-trans retinoic acid (ATRA) for 2 hours.
Project description:The transcriptome of Ctrl and Vitamin A-deficient longterm hematopoietic stem cells (LT-HSC) and multipotant progenitors (MPP3/4) was assessed by RNAseq.
Project description:Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1. Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially of thyroid-stimulating hormone. These findings establish the critical role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
Project description:Pyrydopyrazine A2 induced in vitro the differentiation of leukemic cells (HoxA9-Meis1) into macrophages, we decided to perform a transcriptomic study in order to analyze the GM-CSF pathway regulation. We therefore compared effect with A2 to cells treated with Retinoic acid and D3 Vitamin, a combination known to induce also differentiation of leukemic cells. HoxA9-Meis1 murine AML cells were treated in vitro during 24h, with Pyrydopyrazine( A2) at 3.4μM or a combination of all-trans Retinoic Acid (RA) and 1α-hydroxy-D3 Vitamin (D3V), 10μM each. Gene expression signature was compared to untreated control. One sample was tested for each condition
Project description:Observational studies in human suggest involvement of vitamin A/retinoic acid (RA) signaling in the regulation of airway smooth muscle (ASM) function, but the precise mechanisms by which RA impacts ASM phenotype is not clear. Here, we generated trascriptional profiles from primary human ASM from 3 unrelated donoros cultured in control medium or medium containing BMS493 (an retinoic acid receptor antagonist)
Project description:Vitamin A is an exogenous micronutrient that is derived solely from diet and metabolized into retinoic acid, which acts as an antioxidant and transcriptional regulator. Here we show that obstruction of dietary Vitamin A drives mitochondrial and cell cycle dysfunction in MuSCs and myoblasts that mimics old age. The receptor for vitamin A derived retinol, Stra6, was found to be diminished with MuSC activation and in old age. The loss of Stra6 in myogenic progenitors resulted in accumulation of mitochondrial reactive oxygen species, as well as changes in mitochondrial morphology and respiration. Pharmacological targeting of Stra6 and retinoic acid signaling in myogenic progenitors and aged MuSCs reverted oxidative damage, enhanced mitochondrial function, and improved maintenance of quiescence. These results demonstrate that Vitamin A regulates mitochondria and metabolism in MuSCs to promote quiescence. These results highlight a unique mechanism connecting stem cell function with vitamin intake.
Project description:Vitamin A is an exogenous micronutrient that is derived solely from diet and metabolized into retinoic acid, which acts as an antioxidant and transcriptional regulator. Here we show that obstruction of dietary Vitamin A drives mitochondrial and cell cycle dysfunction in MuSCs and myoblasts that mimics old age. The receptor for vitamin A derived retinol, Stra6, was found to be diminished with MuSC activation and in old age. The loss of Stra6 in myogenic progenitors resulted in accumulation of mitochondrial reactive oxygen species, as well as changes in mitochondrial morphology and respiration. Pharmacological targeting of Stra6 and retinoic acid signaling in myogenic progenitors and aged MuSCs reverted oxidative damage, enhanced mitochondrial function, and improved maintenance of quiescence. These results demonstrate that Vitamin A regulates mitochondria and metabolism in MuSCs to promote quiescence. These results highlight a unique mechanism connecting stem cell function with vitamin intake.