Transcriptional analysis was performed on pre and post excision human induced pluripotent stem cells, the donor human dermal fibroblasts (HDFs) they were derived from and control human embryonic stem cells
Generation and characterization of transgene-free human induced pluripotent stem cells and conversion to putative clinical-grade status.
Specimen part, Cell line
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
View SamplesBackground: Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy regresses pre-existing cardiac hypertrophy, and prevents the progression to heart failure.
Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats.
Sex, Age, Specimen part, Treatment
View SamplesWe used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic mRNA to examine the effect of age on vascular mRNA alterations in the presence and absence of SMC-MR.
Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness With Aging.
Sex, Specimen part
View SamplesProspective isolation is critical to understand the cellular and molecular aspects of stem cell heterogeneity. Here we identify the cell surface antigen CD9 as a novel positive marker that provides a simple alternative for hematopoietic stem cell-isolation at high purity Overall design: mRNA profiles of LT and ST HSCs
The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem cells.
Subject
View SamplesWe demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification.
Specimen part
View Samples8 week-old male C57BL6J mice were given Gram-negative endotoxin (LPS O111:B4, 10 mg/kg) intraperitoneally at time 0. 18 hrs thereafter, they were administered 10 ml/kg 0.9% saline. Mice were sacrificed at 0, 18, or 42 hrs after LPS challenge. Kidneys were immediately collected into TRIzol for RNA preparation. Renal function was measured on blood collected at the time of tissue harvest
PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice.
Sex, Age, Specimen part
View SamplesType I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cellassociated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECMrelated transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.
Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.
Specimen part, Disease, Disease stage, Time
View SamplesThe growth and fruit quality of grapevine are widely affected by abnormal climatic conditions such as water deficit. But how grapevine responds to drought stress is still largely unknown. Here we found that VaNAC26, a member of NAC transcription factor family, was up-regulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardiness wild Vitis species. Ectopic overexpression of VaNAC26 enhanced the drought and salt tolerances in transgenic Arabidopsis. Higher activities of antioxidant enzymes and the lower concentration of H2O2 and O2- were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicate that the reactive oxygen species (ROS) scavenging was enhanced by VaNAC26 in transgenic lines. Microarray based transcriptome analysis reveals that genes related to jasmonic acid (JA) synthesis and signaling were up-regulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on NACRS motif, which was broadly existent in the promoter regions of up-regulated genes in transgenic lines. Endogenous JA content was found increased obviously in VaNAC26-OE-2/3 lines. Our data suggests that VaNAC26 responds to abiotic stresses and may enhance the drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.
Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.
Specimen part
View SamplesSkeletal muscle mass is an important determinant of whole-body glucose disposal. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3'-phosphoinositide–dependent kinase 1 (PDK1), a key component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of exercise load–induced muscle hypertrophy.
Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load.
Sex, Specimen part
View Samples