Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current golden standard pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity
Unraveling a novel transcription factor code determining the human arterial-specific endothelial cell signature.
Specimen partView Samples
Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 352 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF.
Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation.
Specimen part, Treatment, SubjectView Samples
During vertebrate retinogenesis, the precise balance between retinoblast proliferation and differentiation is spatially and temporally regulated through a number of intrinsic factors and extrinsic signaling pathways. Moreover, there are complex gene regulatory network interactions between these intrinsic factors and extrinsic pathways, which ultimately function to determine when retinoblasts exit the cell cycle and terminally differentiate. We recently uncovered a cell non-autonomous role for the intrinsic HLH factor, Id2a, in regulating retinoblast proliferation and differentiation, with Id2a-deficient retinae containing an abundance of proliferative retinoblasts and an absence of terminally differentiated retinal neurons and glia. Here, we report that Id2a function is necessary and sufficient to limit Notch pathway activity during retinogenesis. Id2a-deficient retinae possess elevated levels of Notch pathway component gene expression, while retinae overexpressing id2a possess reduced expression of Notch pathway component genes. Attenuation of Notch signaling activity by DAPT or by morpholino knockdown of Notch1a is sufficient to rescue both the proliferative and differentiation defects in Id2a-deficient retinae. In addition to regulating Notch pathway activity, through an RNA-Seq and differential gene expression analysis of Id2a-deficient retinae, we identify a number of additional intrinsic and extrinsic regulatory pathway components whose expression is regulated by Id2a. These data highlight the integral role played by Id2a in the gene regulatory network governing the transition from retinoblast proliferation to terminal differentiation during vertebrate retinogenesis. Overall design: Two biological replicates for both Id2aMM and Id2aMO samples
Id2a functions to limit Notch pathway activity and thereby influence the transition from proliferation to differentiation of retinoblasts during zebrafish retinogenesis.
No sample metadata fieldsView Samples
Ovarian cancer has a high mortality rate due, in part, to the lack of early detection and incomplete understanding of the origin of the disease. The hen is the only spontaneous model of ovarian cancer, and can therefore aid in the identification and testing of early detection strategies and therapeutics. To our knowledge, no studies to date have examined global gene expression in ovarian cancer of the hen. Our aim was to combine the use of the hen animal model and microarray technology to identify differentially expressed genes in ovarian tissue from normal hens compared to hens with ovarian cancer.
Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin?
Specimen part, Disease, Disease stageView Samples
In the central nervous system (CNS), the microRNAs (miRNAs), small endogenous RNAs exerting a negative post-transcriptional regulation on mRNAs, are involved in major functions, such as neurogenesis, and synaptic plasticity. Moreover, they are essential to define the specific transcriptome of the tissues and cell types. However, few studies were performed to determine the miRNome of the different structures of the rat CNS, even through rat is a major model in neuroscience. We determined the miRNome profile of the hippocampus, the cortex, the striatum, the spinal cord and the olfactory bulb, by small RNA-Seq. We found a total of 365 known miRNAs' and 90 novel miRNAs expressed in the CNS of the rat. Novel miRNAs seemed to be important in defining structure-specific miRNomes. Differential analysis showed that several miRNAs were specifically enriched/depleted in these CNS structures. Then, we correlated miRNAs' expression with the expression of their mRNA targets by mRNA-Seq. This analysis suggests that the transcriptomic identity of each structure is regulated by specific miRNAs. Altogether, these results suggest the critical role played by these enriched/depleted miRNAs in the functional identities of CNS structures. Overall design: miRNA and mRNA profile of 5 structures of the central nervous system of rat, for each structurewe analyzed three biological replicates
Small RNA-Seq reveals novel miRNAs shaping the transcriptomic identity of rat brain structures.
Specimen part, Cell line, SubjectView Samples
Seed germination is a critical developmental process in plant propagation. Knowledge of the gene expression patterns in this critical process is important in order to understand the main biochemical reactions involved in successful germination, specially for economically relevant plants such as Maize.
Expression profile of maize (Zea mays L.) embryonic axes during germination: translational regulation of ribosomal protein mRNAs.
Treatment, TimeView Samples
Copper-based chemotherapeutic compounds Casiopeinas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application.
Whole genome gene expression analysis reveals casiopeína-induced apoptosis pathways.
Cell lineView Samples
An atlas of RNA and protein expression maps across a diverse set of developmental tissues from Zea mays Overall design: RNA-seq collected from a variety of maize tissues
Integration of omic networks in a developmental atlas of maize.
Specimen part, SubjectView Samples
This SuperSeries is composed of the SubSeries listed below.
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Specimen part, TreatmentView Samples