Parathyroid 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 SamplesMost tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regional localization within the bone marrow influences the functional capacity of human HSCs.
Specimen part
View SamplesDemonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution, thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs.
Regional localization within the bone marrow influences the functional capacity of human HSCs.
Specimen part
View SamplesDemonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution, thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs.
Regional localization within the bone marrow influences the functional capacity of human HSCs.
Specimen part
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer.
Cell line
View SamplesAnalysis of AR-regulation of gene expression. The hypothesis tested in the present study was that AR influences the expression of genes that participate in important bioprocesses in prostate cancer cells, including cell cycle, DNA replication, recombination and repair. Results provide important information on AR-responsive genes that may be crucial to the cell survival and the progression of prostate cancer.
Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer.
Cell line
View SamplesAnalysis of c-Myb-regulation of gene expression. The hypothesis tested in the present study was that c-Myb influences the expression of specific sets of genes that are involved in cell cycle, DNA replication, recombination and repair. Results provide important information on c-Myb-responsive genes that may be crucial to the cell survival and the progression of prostate cancer.
Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer.
Cell line
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View Samples