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: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:The effects of retinoic acid/vitamin A signal on the transcriptional profile of the ductus arteriosus during development were examined. Keywords: time course, development, response to a nutritional agent
Project description:It has been demonstrated that vitamin C enhances reprogramming efficiency during inducing pluripotent stem cells, however, the underlying mechanisms are not fully understood. To find the downstream target genes of vitamin C and investigate the mechanism of vitamin C on reprogramming promotion, we performed Microarray analyses to identify its downstream targets. Retinoic acid (RA), a stimulus molecule for cellular differentiation, is set as negative control. The data show the genes regulated by vitamin C or RA.
Project description:Many asexually-propagating marine invertebrates can survive extreme environmental conditions by developing dormant structures, i.e., morphologically simplified bodies that retain the capacity to completely regenerate a functional adult when conditions return to normal. Here, we examine the environmental, morphological, and molecular characteristics of dormancy in two distantly related clonal tunicate species: Polyandrocarpa zorritensis and Clavelina lepadiformis. In both species, we report that the dormant structures are able to withstand harsher temperature and salinity conditions compared to the adult, and are the dominant forms these species employ to survive the colder winter months. By finely controlling the entry and exit of dormancy in laboratory-reared individuals, we were able to select and characterize the morphology of dormant structures associated with their transcriptome dynamics. In both species, we identified putative stem and nutritive cells in structures that resemble the earliest stages of asexual propagation. By characterizing gene expression during dormancy and regeneration into the adult body plan (i.e., germination), we observed that genes which control dormancy and environmental sensing in other metazoans, notably HIF-α and insulin signaling genes, are also expressed in tunicate dormancy. Germination-related genes in these two species, such as the retinoic acid pathway, are also found in other unrelated clonal tunicates during asexual development. These results are suggestive of repeated exaptation of conserved eco-physiological and regeneration programs for the origin of novel dormancy-germination processes across distantly related animal taxa.