Developmental neuronal remodeling is an evolutionarily conserved mechanism required for accurate wiring of mature nervous systems. Despite its fundamental role in neurodevelopment and proposed contribution to various neuropsychiatric disorders, the mechanisms instructing remodeling are only partially known. Here, we uncover the fine temporal transcriptional landscape of a stereotypic remodeling event - that of the Drosophila mushroom body ? neurons. To enrich and complement this developmental expression atlas, we also sequenced developing ? neurons perturbed for three key transcription factors known to regulate pruning. Together, these datasets allowed us to construct the developmental and temporal framework of transcriptional modules that together drive remodeling. Moreover, we identified 10 DNA binding proteins that are involved in various aspects of remodeling, and describe their hierarchical relationships. Overall, this study provides the first broad and detailed molecular insight into the complex regulatory dynamics of developmental neuronal remodeling. Overall design: Transcriptional profiling of drosophila ? neurons during development and when perturbed by EcR-DN, E75 RNAi or Sox14 RNAi. Other adult neurons and astrocyte-like cells also sequenced.
Combining Developmental and Perturbation-Seq Uncovers Transcriptional Modules Orchestrating Neuronal Remodeling.
Specimen part, Cell line, Subject
View SamplesHow cells acquire their fate is a fundamental question in both developmental and regenerative biology. Multipotent progenitors undergo gradual cell fate restriction in response to temporal and positional cues from the microenvironment, the nature of which is far from being clear. In the case of the lymphatic system, venous endothelial cells are thought to give rise to lymphatic vessels, through a process of trans-differentiation. Upon expression of a set of transcription factors, venous cells acquire a lymphatic fate, and bud out to generate the lymphatic vasculature. In this work we challenge this view and show that while lymphatic endothelial cells (LECs) do arise in the Cardinal Vein (CV), they do so from a previously uncharacterized pool of multipotent angioblasts. Using lymphatic-specific transgenic zebrafish, in combination with endothelial photoconvertible reporters, and long-term live imaging, we demonstrate that these multipotent angioblasts can generate not only lymphatic, but also arterious, and venous fates. We further reveal that the underlying endoderm serves as a source of Wnt5b, which acts as a lymphatic inductive signal, promoting the angioblast-to-lymphatic transition. Moreover, Wnt5b induced lymphatic specification in human embryonic stem cells- derived vascular progenitors, suggesting that this process is evolutionary conserved. Our results uncover a novel mechanism of lymphatic vessel formation, whereby multipotent angioblasts and not venous endothelial cells give rise to the lymphatic endothelium, and provide the first characterization of their inductive niche. More broadly, our findings highlight the CV as a plastic and heterogeneous structure containing different cell populations, analogous to the hematopoietic niche in the aortic floor. Overall design: Following Kaede photoconversion of dorsal or ventral halves of the PCV in Tg(fli1:gal4;uasKaede) embryos at 24 hpf, 6Â embryos per group were used for FACS isolation of Kaede photconverted (red) ECs.
Lymphatic vessels arise from specialized angioblasts within a venous niche.
No sample metadata fields
View SamplesWe identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Age, Specimen part, Race, Subject, Time
View SamplesWe identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis.
Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.
Age, Specimen part, Race, Subject
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View SamplesRNA-Seq analysis of SSA treated cells Overall design: HeLa cells, nuclear and cytoplasmic fractions, treated with SSA or MeOH
Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.
No sample metadata fields
View SamplesIn mouse models, the bromodomain PHD finger transcription factor (BPTF) chromatin remodeling subunit in tumor cells suppresses natural killer (NK) cell antitumor activity.
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Specimen part, Cell line
View SamplesDepleting the NURF chromatin remodeling complex results in enhanced antitumor immunity using mouse tumor models syngenic to two strain backgrounds.
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Specimen part
View SamplesOverarching aim is to achieve a greater understanding of the control of progenitor cells within the adult human retina within the normal and diseased retinal microenvironment. Specifically we will assess via our experimental designs: (i) the control of CD133+ retinal cell populations that display mitotic potential and differentiation and
CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF).
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.
Sex, Specimen part
View Samples