Light initiates the seedling deetiolation transition by promoting major changes in gene expression mainly regulated by phytochrome (phy) photoreceptors. During the initial dark-to-light transition, phy photoactivation induces rapid changes in gene expression that eventually lead to the photomorphogenic development. Recent reports indicate that this process is achieved by phy-induced degradation of Phy-Interacting bHLH transcription Factors (PIFs) PIF1, PIF3 PIF4 and PIF5, which are partly redundant constitutive repressors of photomorphogenesis that accumulate in darkness. In order to test whether light/phy-regulated gene expression occurs through these PIFs, we have performed whole-genome expression analysis in the pif1pif3pif4pif5 quadruple mutant (pifq).
Definition of early transcriptional circuitry involved in light-induced reversal of PIF-imposed repression of photomorphogenesis in young Arabidopsis seedlings.
No sample metadata fields
View SamplesRNA-seq experiment of WT and pifq mutant seedlings grown for 3 days in darkness in presence or absence of Lincomycin. Overall design: Transcriptome profiles of the wild-type (WT) and pif1pif3pif4pif5 (pifq) quadruple mutant seedlings grown for 3 days in the dark in presence or absence of Lincomycin. Biological triplicate samples were analyzed from libraries constructed using a 3''-capture, 5'' to 3'' directional method.
Phytochrome and retrograde signalling pathways converge to antagonistically regulate a light-induced transcriptional network.
Subject
View SamplesPlants respond to changes in the red:far red ratio (R:FR) of incident light. A reduction in this ratio (increase in FR) results in the Shade Avoidance Response (SAR) with associated changes in gene expression. The Phyotchrome-Interacting Factors (PIFs) are bHLH transcription factors known to be involved in the SAR. An analysis of changes in gene expression in WT and quadruple pif1pif3pif4pif5 (pifq; Leivar et al., 2008 (PMID 19920208)) mutant seedlings in response to an increase in FR should identify primary targets of PIF signaling.
Dynamic antagonism between phytochromes and PIF family basic helix-loop-helix factors induces selective reciprocal responses to light and shade in a rapidly responsive transcriptional network in Arabidopsis.
Specimen part
View SamplesPIF3 plays a role as repressor of photomorphogenesis in darkness. To identify PIF3-regulated genes that might be implementing this action, we have performed whole-genome expression analysis in the pif3 mutant.
Functional profiling identifies genes involved in organ-specific branches of the PIF3 regulatory network in Arabidopsis.
Specimen part
View SamplesRecent efforts have uncovered immense transcriptional and ontogenetic diversity among tissue-resident macrophages, each with their own transcriptional profile endowing the cell with its tissue-specific functions. However, it is currently unknown whether the origins of different macrophage populations may affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone marrow-derived macrophages (BMDM) are even present in tumors of the brain, a tissue where there is no homeostatic involvement of peripherally-derived myeloid cells. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing models to demonstrate that BMDM are indeed abundant in primary and metastatic brain tumors. Transcriptional profiling of tumor-associated BMDM and resident microglia showed that these cells acquire substantially different gene expression profiles. Our data suggest that transcriptional networks in each cell population are associated with tumor-mediated education, yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between brain-resident microglia and peripherally-derived macrophages in both primary and metastatic disease in mouse and human. Overall design: Tumor associated microglia and macrophages were isolated from mouse glioma tumors. Samples are provided as matched microglia and macrophages from 3 tumors.
Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.
Specimen part, Cell line, Subject
View SamplesGlioblastoma multiforme (GBM), the most common and aggressive primary brain tumor in adults, can be divided into several molecular subtypes including proneural GBM. Most clinical strategies aimed at directly targeting glioma cells in these tumors have failed. A promising alternative is to target stromal cells in the brain microenvironment, such as tumor-associated microglia and macrophages (TAMs). Macrophages are dependent upon colony stimulating factor (CSF)-1 for differentiation and survival; therefore, we used an inhibitor of its receptor, CSF-1R, to target macrophages in a mouse proneural GBM model. CSF-1R inhibition dramatically increased survival in mice and regressed established GBMs. Tumor cell apoptosis was significantly increased, and proliferation and tumor grade markedly decreased. Surprisingly, TAMs were not depleted in tumors treated with the CSF-1R inhibitor. Instead, analysis of gene expression in TAMs isolated from treated tumors revealed a decrease in alternatively activated/ M2 macrophage markers, consistent with impaired tumor-promoting functions. These gene signatures were also associated with better survival specifically in the proneural subtype of patient gliomas. Collectively, these results establish macrophages as valid therapeutic targets in proneural gliomas, and highlight the clinical potential for CSF-1R inhibitors in GBM.
CSF-1R inhibition alters macrophage polarization and blocks glioma progression.
Sex, Specimen part
View SamplesThe inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes. Overall design: Cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarcted and non-infarcted neonatal (P1) and adult (P56) hearts were isolated by enzymatic dissociation and FACS. RNA sequencing (RNA-seq) was performed on these cell populations to generate a transcriptomic atlas of the major cardiac cell populations during cardiac development, repair and regeneration. In addition, we surveyed the epigenetic landscape of cardiomyocytes during post-natal maturation by performing deep sequencing of accessible chromatin regions using the Assay for Transposase-Accessible Chromatin (ATAC-seq) from purified cardiomyocyte nuclei (P1, P14 and P56).
Multicellular Transcriptional Analysis of Mammalian Heart Regeneration.
Specimen part, Treatment, Subject
View SamplesThe pathology of chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and the majority of lung cancers involve the small airway epithelium (SAE), the single continuous layer of cells lining the airways ?6th generations. The basal cells (BC) are the stem/progenitor cells of the SAE, responsible for the differentiation into intermediate cells and ciliated, club and mucous differentiated cells. To facilitate the study of the biology of the human SAE in health and disease, we immortalized and characterized a normal human SAE basal cell line.
Characterization of an immortalized human small airway basal stem/progenitor cell line with airway region-specific differentiation capacity.
Sex, Age, Specimen part, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
No sample metadata fields
View SamplesThe complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples.
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
No sample metadata fields
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