Elimination of peripheral retinal axons leads to changes in gene expression in both visual and somatosensory thalamic neurons.
Prenatal thalamic waves regulate cortical area size prior to sensory processing.
Specimen part
View SamplesBone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization.
A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.
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View SamplesWe develop a theoretical-computational framework for inferring cell state transition dynamics, and apply it to mouse embryonic stem cells states defined by expression levels of Esrrb, Tbx3, and Zscan4. RNA-seq was performed to characterize the larger transcriptional differences between states expressing combinations of these three specific genes, and proceed to explore their dynamic interconversion. Overall design: A double knock-in reporter for Esrrb and Tbx3 with distinct fluorescent proteins was constructed to enable purification of substates defined by their relative expression levels (Esrrb-/Tbx3-; Esrrb+/Tbx3-; Esrrb+/Tbx3+). A second line was constructed using a promoter-fragment reporter to isolate Zscan4+ from Zscan4- cells. Following FACS isolation, the subpopulations were sequenced on an Illumina HiSeq2500. Biological replicates were collected on different days.
Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements.
Specimen part, Subject
View SamplesThese data consist of an expression survey of three receptor cell lines and the parental cell types was performed to determine expression of BMP related genes. Overall design: Sequence libraries for three cell types were constructed using NEBNext Ultra RNA-seq (NEB #E7530) and sequenced on Illumnia HiSeq2500.
Combinatorial Signal Perception in the BMP Pathway.
Cell line, Subject
View SamplesIn contrast to the migration of leukocytes from blood vessels into tissues, and the involvement of adhesion molecules and chemokines in this process, the migration of leukocytes from the tissue into lymphatic vessels is much less well understood. This can, in part be explained by the fact that murine lymphatic endothelial cells (LECs) have proven particularly hard to isolate and propagate in culture. Hence, it has been difficult to establish suitable models to study this process in vitro. Combining magnetic bead-based purification and fluorescence-activated cell sorting (FACS), we have isolated LECs (immorto-LECs) from the skin of mice which express a temperature-sensitive SV40 large T antigen (H-2Kb-tsA58 mice; ImmortoMice) in all cell types under the control of the MHC-class-I-promotor, H-2Kb. The isolated cells are viable for more than 30 passages when cultured at 33 C, the temperature at which the large T antigen is stably expressed. Furthermore, immorto-LECs tolerate several days of culture at 37 C, but become senescent if continuously cultured at this temperature. All cells stably express endothelial and lymphatic markers like CD31, podoplanin, Prox-1 and VEGFR-3 up to passage 30. When cultured in presence of tumor necrosis factor-alpha (TNF-a), immorto-LECs upregulate adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin, similarly to what has been reported to occur under inflammatory conditions in vivo. Overall, our findings establish immorto-LECs as a useful and handy tool for the in vitro investigation of immune cell transmigration across lymphatic endothelium.
Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner.
Specimen part
View SamplesDietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4a-related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat-2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62mutants. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span. Overall design: Young adult worms before bearing eggs inside were collected. N2 serves as the control of wild type. 3 biological replicates included in this experiment.
Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.
Subject
View SamplesWe performed RNA-seq analysis of WT and blmp-1(tm548) mutant L3 larvae to identify genes regulated by the zing-finger transcription factor BLMP-1. Overall design: We analyzed three WT and three blmp-1 mutant biological replicates
DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.
Cell line, Subject
View SamplesIn dense stands,the earliest neighbor response is induced by touching,leading to shade avoidance. During light competion the R:FR distribution is not homogenous, leading to local differences in light quality (R:FR) within the same leaf. Hyponasty is induced by FR-signaling in the lamina tip, which then induces local cell growth in the petiole base. Likewise, local touching of the leaf tip induces a similar phenoype.
Neighbor detection at the leaf tip adaptively regulates upward leaf movement through spatial auxin dynamics.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
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