Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA264319 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:By chemical modulation of the PKA/CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA/CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors and is dependent on secreted BMP ligands through the type I BMP receptor. We used microarray to document upregulation of PKA/CREB-BMP pathway as well as global BMP target upregulation upon PKA/CREB activation. Isolated VE+ cells from E11.5 AGM were treated with BMP4 (4ng/ml), forskolin (25uM) or both for 8 hours before RNA isolation.
2015-03-30 | E-GEOD-62517 | biostudies-arrayexpress
Project description:By chemical modulation of the PKA/CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA/CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors and is dependent on secreted BMP ligands through the type I BMP receptor. We used microarray to document upregulation of PKA/CREB-BMP pathway as well as global BMP target upregulation upon PKA/CREB activation.
2015-03-30 | GSE62517 | GEO
Project description:Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. In transplantation assays of hematopoietic reconstitution, we find that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at E9.5 not previously described to harbor HSCs. Effects on hematopoiesis appear to be mediated in part by prostaglandin E2 (PGE2) and the cyclic AMP-protein kinase A (cAMP-PKA) signaling axis. Studies of Ncx1 cardiac mutants corroborate that blood flow is required for sufficient COX2 levels and phosphorylation of CREB. Further implicating PGE2 in mediating the effects of shear stress, we find that E10.5 and E11.5 AGM treated transiently with the synthetic analog dmPGE2 engraft more robustly and contribute to greater lymphoid reconstitution. These data provide a mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential. -
2015-04-05 | GSE62463 | GEO
Project description:A mouse AGM-derived cell line, AGM-s3, was shown to support the development of hematopoietic stem cells. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-s3, some of which were hematopoiesis supportive (s3-A9) and others which were non-supportive (s3-A7), and we analyzed the gene expression profiles by gene chip analysis. Experiment Overall Design: Genome-wide gene expression was examined using Affymetrix GeneChip array. Assays were performed according to the manufacturer's protocol. Total RNA was isolated from each stromal cell lines. We analysed 3 cell lines, AGM-s3-A9, AGM-s3-A7 and OP9. AGM-s3-A9 and OP9 are hematopoiesis supportive cell lines. AGM-s3-A7 is a hematopoiesis non-supportive cell line.
2008-10-26 | E-GEOD-11891 | biostudies-arrayexpress
Project description:Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.
2023-09-28 | PXD045747 | JPOST Repository
Project description:Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.
2023-09-26 | PXD045674 | JPOST Repository
Project description:Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. In transplantation assays of hematopoietic reconstitution, we find that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at E9.5 not previously described to harbor HSCs. Effects on hematopoiesis appear to be mediated in part by prostaglandin E2 (PGE2) and the cyclic AMP-protein kinase A (cAMP-PKA) signaling axis. Studies of Ncx1 cardiac mutants corroborate that blood flow is required for sufficient COX2 levels and phosphorylation of CREB. Further implicating PGE2 in mediating the effects of shear stress, we find that E10.5 and E11.5 AGM treated transiently with the synthetic analog dmPGE2 engraft more robustly and contribute to greater lymphoid reconstitution. These data provide a mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential. - AGM from C57BL/6J embryos at 10.5 days gestation (E10.5) were isolated by microdissection from uteri of pregnant dams, following by gentle dissociation by Accutase with agitation at room temperature for 20 minutes. Single cell suspension was seeded on microfluidic IBIDI VI^0.4 6-channel slides (0.8 to 1x10^7 cells per channel) and permitted to attach for 8 hours. Fluid movement was then applied to each channel using a Harvard Apparatus PHD ULTRA programmable syringe pump for manangement of M5300 Myelocult medium. Cells were exposed either to static/low flow (0.0001 dyne/cm^2) or wall shear stress (WSS) of 5 dyne/cm^2 for 6 hours or 36 hours. In addition, some cells were treated with 10 uM indomethacin (indo) to inhibit COX2 activity and PGE2 synthesis. Upon collection of cells with RLT lysis buffer (QIAGEN RNeasy kit), six channels of identical treatment were pooled to comprise a single sample. 24 samples total are included in this study. 12 samples were collected after 6 hours and 12 after 36 hours. In detail, samples included at 6 hours: 3 static, 3 static with indo, 3 WSS, 3 WSS with indo; and at 36 hours: 3 static, 3 static with indo, 3 WSS, 3 WSS with indo. Sample labels begin with the timepoint collected and end with the replicate number, i.e., 06WSS1 for the 6 hour collection of the first replicate of the WSS sample.
2015-04-05 | E-GEOD-62463 | biostudies-arrayexpress
Project description:The first HSCs are produced in the aorta-gonadmesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture. Embryonic day 11 AGM are dissected and either analyzed directly, or after explant culture in conditions containing BMP/Hedgehog with or without cyclopamine. EC: endothelial enriched (CD31+Kit-); MC: mesenchymal cell enriched (CD31-Kit-); HPSC: hematopoietic progenitor/stem cell enriched; AGM11: E11 fresh AGMs; AGMex: AGM after explant culture; AGMcy: AGM after explant in presence of cyclopamine; CD31p: CD31 positive; CD31n: CD31 negative; KITp: c-Kit positive; KITn: c-Kit negative; BREp: BRE-GFP positive; BREn: BRE-GFP negative
2015-12-22 | E-GEOD-76253 | biostudies-arrayexpress
Project description:A mouse AGM-derived cell line, AGM-s3, was shown to support the development of hematopoietic stem cells. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-s3, some of which were hematopoiesis supportive (s3-A9) and others which were non-supportive (s3-A7), and we analyzed the gene expression profiles by gene chip analysis. Keywords: cell type comparison
2008-10-10 | GSE11891 | GEO
Project description:Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.
2023-08-02 | GSE239572 | GEO