Herein, we investigated eMSC and eSF freshly isolated from endometrium from women with and without endometriosis and compared them to their respective short- and long-term cultures and subsequent decidualization response to progesterone.
Human Endometrial Fibroblasts Derived from Mesenchymal Progenitors Inherit Progesterone Resistance and Acquire an Inflammatory Phenotype in the Endometrial Niche in Endometriosis.
Age, Specimen part, Disease
View SamplesMesenchymal stem cells (eMSC) from perimenopausal (PeriM) endometrium do not exhibit significantly different transcriptomes from their premenopausal (PreM) counterparts, but PeriM endometrial stromal fibroblasts (eSF) demonstrate altered pathway activation.We compared transcriptomes of PeriM and PreM eSF, investigated if eMSC persist in PeriM endometrium, and whether eMSC and eSF undergo changes as a result of the perimenopausal endocrine milieu.Endometrium was obtained from 9 PeriM and 9 PreM women. Microarray analysis was performed on FACS-isolated eSF and eMSC and data were validated by quantitative RT-PCR. eMSC were immuofluorescently localized to the perivascular region of PeriM endometrium.Principal component analysis showed that cells clustered into three distinct groups in 3-dimensional space: PeriM eMSC and PreM eMSC clustered together, while PeriM eSF and PreM eSF formed two discrete clusters separate from eMSC. Hierarchical clustering revealed a branching pattern consistent with the PCA results, indicating that eMSC from PreM and PeriM women exhibited a similar transcriptomic signature. Pathway analysis revealed dysregulation of cytoskeleton, proliferation, and survival pathways in PeriM vs. PreM eSF. A number of small nucleolar RNAs were also differentially regulated in PeriM eSF.Cell populations have altered gene expression in PeriM vs. PreM endometrium. While eMSC populations exhibited similar transcriptomes, PeriM eSF had altered pathway activation when compared to PreM eSF. This study provides insight into aging endometrium with relevance to function, including pregnancy establishment in reproductively older women.
No associated publication
Age, Specimen part, Disease
View SamplesMaintenance of central nervous system (CNS) homeostasis requires tight regulation over the metabolites, drugs, cells, and pathogens entering the brain. The blood-brain barrier (BBB) carries out these functions, but the regulatory mechanisms underlying BBB physiology are not completely understood. In addition, the BBB has long been an obstacle to the pharmacologic treatment of CNS diseases, thus molecular model systems that can parse BBB functions and understand the complex integration of sophisticated cellular anatomy and highly polarized chemical protection physiology are desperately needed.
No associated publication
Specimen part
View SamplesThe blood-brain barrier (BBB) is an evolutionary conserved tissue interface that possesses potent chemical protection properties functioning to strictly modulate the central nervous system (CNS) microenvironment. These same properties, including tight cellular junctions and efflux transporters, also limit access of CNS-active pharmaceuticals. For this reason, understanding the molecular mechanisms that regulate BBB chemical protection is of great biomedical interest. The BBB of Drosophila consists of two surface glia layers that completely surround the brain. This tissue interface contains both tight cellular junctions (termed septate junctions) and drug efflux transporters; thus, the Drosophila BBB can potentially serve as a model for understanding complex regulation of BBB physiology.
No associated publication
Sex, Specimen part
View SamplesIn humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of pre-term delivery, hemorrhage and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along the scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The mRNA encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly differentially expressed molecule in PAS samples. Over-expression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up regulate a cancer-like pro-invasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.
Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum.
Specimen part, Disease
View SamplesAbstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling.
Global Transcriptome Abnormalities of the Eutopic Endometrium From Women With Adenomyosis.
Age, Specimen part, Disease
View SamplesThe Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown.
Early postmyocardial infarction survival in Murphy Roths Large mice is mediated by attenuated apoptosis and inflammation but depends on genetic background.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells.
Cell line, Time
View SamplesTotal RNA microarray data from Fresh-Frozen Glioblastoma tumor samples.
Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas.
Specimen part, Disease stage
View SamplesHigh-fat diet (HFD) in normoxia causes a worsened phenotype in adult female flies compared to regular diet (RD). Intermittent hypoxia (IH) causes an opposite phenotype both when flies are on RD in IH compared to normoxia and even more dramatically when on HFD in IH compared to HFD in normoxia.
No associated publication
Sex, Specimen part
View Samples