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GSE67827
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cancer incidence increases in the elderly, although the underlying reasons for this association are unknown. We show that B-progenitors in old mice exhibit profound signaling and metabolic defects, and that expression of BCR-ABL, NRASV12 and MYC reverses these fitness defects, leading to selection of oncogenically-initiated cells and leukemogenesis in old hematopoietic backgrounds. Aging is associated with increased inflammation in the BM microenvironment, and inducing inflammation in young mice phenocopies aging B-lymphopoiesis. Importantly, reducing inflammation in aged mice preserves the function of B-progenitors and prevents NRasV12-mediated oncogenesis. We conclude that chronic microenvironments in old age lead to reductions in the fitness of hematopoietic stem and progenitor cell populations. This reduced progenitor pool fitness leads to selection for cells harboring oncogenic mutations in part due to their ability to correct aging-associated functional defects.
Publication Title
Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In the current study, we hypothesized that if bone-marrow derived MSC contribute to endometrial regeneration and are progenitors to hESF, their treatment with agents known to regulate hESF differentiation could promote their differentiation down the stromal fibroblast lineage. To this end, we treated bone marrow-derived MSC with estradiol (E2) and progesterone (P4), BMP2, and activators of the PKA pathway and investigated specific markers of hESF differentiation (decidualization). Furthermore, we investigated the transcriptome of these cells in
Publication Title
The bone marrow-derived human mesenchymal stem cell: potential progenitor of the endometrial stromal fibroblast.
Sample Metadata Fields
Specimen part
View Samples- Glycine max
- 26 Downloadable Samples
Illumina HiSeq 2000
Description
Soybean (Glycine max) seeds are an important source of seed storage compounds, including protein, oil, and sugar used for food, feed, chemical, and biofuel production. We assessed detailed temporal transcriptional and metabolic changes in developing soybean embryos to gain a systems biology view of developmental and metabolic changes and to identify potential targets for metabolic engineering. Two major developmental and metabolic transitions were captured enabling identification of potential metabolic engineering targets specific to seed filling and to desiccation. The first transition involved a switch between different types of metabolism in dividing and elongating cells. The second transition involved the onset of maturation and desiccation tolerance during seed filling and a switch from photoheterotrophic to heterotrophic metabolism. Clustering analyses of metabolite and transcript data revealed clusters of functionally related metabolites and transcripts active in these different developmental and metabolic programs. The gene clusters provide a resource to generate predictions about the associations and interactions of unknown regulators with their targets based on guilt-by-association relationships. The inferred regulators also represent potential targets for future metabolic engineering of relevant pathways and steps in central carbon and nitrogen metabolism in soybean embryos and drought and desiccation tolerance in plants. Overall design: Total mRNA profiles of 10 time course samples of Soybean developing embryos with three replicates per sample were generated by deep sequencing, using Illumina HiSeq 2000
Publication Title
Transcriptome-wide functional characterization reveals novel relationships among differentially expressed transcripts in developing soybean embryos.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The implantation process begins with attachment of the trophectoderm (TE) of the blastocyst to the maternal endometrial epithelium. Herein we have investigated the transcriptome of mural TE cells from 13 human blastocysts and compared these with those of human embryonic stem cell (hESC)-derived-TE (hESCtroph). The transcriptomes of hESFtroph at days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted proteins of the TE of human blastocysts and of hESCtroph are several molecules known to be involved in the implantation process as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, Wnt 5A, follistatin. The similarities between the two lineages underscore some of the known mechanisms and offer discovery of new mechanisms and players in the process of the very early stages of human implantation. We propose that the hESCtroph is a viable functional model of human trophoblasts to study trophoblast-endometrial interactions. Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics aimed at practical challenges in human infertility and pregnancy disorders associated with abnormal embryonic implantation.
Publication Title
Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Intrinsic abnormalities in transplanted eutopic endometrium are believed to contribute to the pathogenesis of pelvic endometriosis. Herein, we investigated transcriptomic differences in human endometrial stromal fibroblasts (hESF) from women with (hESFendo) versus without (hESFnon-endo) endometriosis, in response to activation of the PKA pathway with 8-Br-cAMP. hESFnon-endo (n=4) and hESFendo (mild endometriosis, n=4) were isolated from eutopic endometrium and treated +/- 0.5mM 8-Br-cAMP for 96 hours. Purified total RNA was subjected to microarray analysis using the whole genome Gene 1.0 ST Affymetrix platform. 733 genes were regulated in cAMP-treated hESFnon-endo versus 172 genes in hESFendo, suggesting a blunted response to cAMP/PKA pathway activation in women with disease. Real-time PCR and ELISA validated the decreased expression of decidualization markers in hESFendo compared to hESFnon-endo. In the absence of disease, 8-Br-cAMP down-regulated progression through the cell-cycle due to a decrease in Cyclin D1, cyclin-dependent kinase 6 and cell division cycle 2, and an increase in cyclin-dependent kinase inhibitor 1A. However, cell cycle components in hESFendo were not responsive to 8-Br-cAMP, resulting in persistence of a proliferative phenotype. hESFendo treated with 8-Br-cAMP exhibited altered expression of immune response, extracellular matrix, cytoskeleton, and apoptosis genes. Changes in phosphodiesterase expression and activity were not different among experimental groups. Thus, eutopic hESF with increased proliferative potential may seed the pelvic cavity via retrograde menstruation and promote establishment, survival, and proliferation of endometriosis lesions, independent of hydrolysis of cAMP and likely due to an inherent abnormality in the PKA pathway in the presence of disease.
Publication Title
The protein kinase A pathway-regulated transcriptome of endometrial stromal fibroblasts reveals compromised differentiation and persistent proliferative potential in endometriosis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 M) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis.
Publication Title
Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
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. 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.
Publication Title
Global Transcriptome Abnormalities of the Eutopic Endometrium From Women With Adenomyosis.
Sample Metadata Fields
Age, Specimen part, Disease
View Samples- Rattus norvegicus
- 5 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
C-peptide exerts beneficial effects on glomerular hyperfiltration in type I diabetic patients. As C-peptide localizes to the nucleus, we investigated the transcriptional activities of C-peptide in proximal tubular cells isolated from diabetic rats.
Publication Title
Early transcriptional regulation by C-peptide in freshly isolated rat proximal tubular cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A population of endometrial cells displaying key properties of mesenchymal stem cells (eMSC) has been identified in human endometrium. eMSC co-express CD146 and PDGFRB surface markers, have a perivascular location, and likely represent the reservoir of progenitors giving rise to the endometrial stromal fibroblast lineage. Endometrial stromal cells isolated from 16 oocyte donors and 3 benign gynecologic surgery subjects were FACS sorted into four populations: CD146+/PDGFRB+ (eMSC); CD146+/PDGFRB- (endothelial cells); CD146-/PDGFRB+ (stromal fibroblasts); CD146-/PDGFRB- (mixed population) then subjected to gene expression analysis on Affymetrix Human Gene 1.0 ST arrays, and differentially expressed genes compared between eMSC, stromal fibroblast, and endothelial cell populations. Ninety-two genes were validated by multiplex quantitative RT-PCR on seventy of these sorted cell populations. Immunohistochemistry was used to verify the perivascular location of eMSCs.Principal component analysis and hierarchical clustering showed eMSC clustering discretely near stromal fibroblasts and separately from endothelial cells. eMSC expressed pericyte markers and genes involved hypoxia response, inflammation, proteolysis, and angiogenesis/vasculogenesis all relevant to endometrial tissue breakdown and regeneration. Additionally, eMSC displayed distinct gene profiles for cell-cell communication and regulation of gene expression. Overall, the phenotype of the eMSC is that of a multipotent pericyte responsive to hypoxic, proteolytic, and inflammatory stimuli, able to induce angiogenesis, migrate and differentiate into lineage cells, and potentially respond to estradiol and progesterone. Identifying the pathways and gene families described herein in the context of the endometrial niche, will be valuable in understanding normal and abnormal endometrial development in utero and differentiation in adult uterus.
Publication Title
Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hopx is a transcription co-factor expressed during lung development and we wanted to profile Hopx +/+ and -/- embyonic lungs. Results inform the role of Hopx in embryonic lung development
Publication Title
Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.
Sample Metadata Fields
Specimen part
View Samples