Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the global abundance of transcripts, proteins and metabolites along the proximodistal axis of caudal fins of uninjured and regenerating adult zebrafish. Using this approach, we uncovered complex overlapping expression patterns for hundreds of molecules involved in diverse cellular functions, including developmental and bioelectric signaling as well as amino acid and lipid metabolism. Moreover, 32 genes differentially expressed at the RNA level had concomitant differential expression of the encoded proteins. Thus, the identification of proximodistal differences in levels of RNAs, proteins, and metabolites will facilitate future functional studies of positional memory during appendage regeneration. Overall design: RNA-seq was performed on 5 biological replicates for each of 3 positions along the proximodistal axis of the caudal fin; proximal, middle and distal (15 total samples). Each biological replicate was a pool of fin regions cut from 2 male and 2 female zebrafish.
Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish.
No sample metadata fields
View SamplesWe used the Affymetrix GeneChip Mouse Genome 430 2.0 Arrays to compare the gene expression profiles of wildtype and miR-146a-deficient 2D2 transgenic T cells.
miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity.
Specimen part
View SamplesHigh-density lipoproteins (HDLs) protect pancreatic cells against apoptosis. This property might be related to the increased risk to develop diabetes in patients with low HDL blood levels. However, the mechanisms by which HDLs protect cells are poorly characterized. Here we use a transcriptomic approach to identify genes differentially modulated by HDLs in cells subjected to apoptotic stimuli.
Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta-cells.
Specimen part, Cell line
View SamplesMouse lung CD11c+ dendritic cells are composed of 2 major DC subsets, the CD103+CD11b-low/intermediate DC (CD103+ DC) and the CD11b-highCD103- DC (CD11b-high DC). These 2 subsets are functionally distinct. Comparison of their functions showed CD103+ DC
Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.
Specimen part
View SamplesExtensive molecular profiling of leukemias and preleukemic diseases has revealed that distinct clinical entities, like acute myeloid (AML) and T-lymphoblastic leukemia, share the same pathogenetic mutations. It is not well understood how the cell of origin, accompanying mutations, extracellular signals or structural differences in a mutated gene determine the phenotypic identity of the malignant disease. We studied the relationship of different protein domains of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. We found that the most C-terminal domain of MN1 was required to block myeloid differentiation at an early stage, and deletion of an extended C-terminal domain resulted in loss of myeloid identity and cell differentiation along the T-cell lineage in vivo. Megakaryocytic/erythroid lineage differentiation was blocked by the most N-terminal domain. In addition, the N-terminus was required for proliferation and leukemogenesis in vitro and in vivo through upregulation of HoxA9, HoxA10 and Meis2. Our results provide evidence that a single oncogene can modulate cellular identity of leukemic cells based on its active domains. It is therefore likely that different mutations in the same oncogene may impact cell fate decisions and phenotypic appearance of malignant diseases.
Cell fate decisions in malignant hematopoiesis: leukemia phenotype is determined by distinct functional domains of the MN1 oncogene.
Specimen part
View SamplesIn this study, we have explored microarray-based differential gene expression profile in mouse lung tissue 8 h after inducing polymicrobial sepsis and the effect of preprotachykinin-A (PPTA) gene deletion. A range of genes differentially expressed (> 2-fold) in microarray analysis was assessed, PPTA-knockout septic mice with their respective sham controls.
Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.
Specimen part, Treatment
View SamplesMitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Cell line, Treatment
View SamplesAlthough Notch signaling has been clearly implicated in lymphoid differentiation, its role in myeloid lineages differentiation is unclear.
Notch signaling specifies megakaryocyte development from hematopoietic stem cells.
No sample metadata fields
View SamplesAcute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver
Gene ontology mapping as an unbiased method for identifying molecular pathways and processes affected by toxicant exposure: application to acute effects caused by the rodent non-genotoxic carcinogen diethylhexylphthalate.
Sex, Specimen part, Compound, Time
View SamplesOld C57BL/6 mice cannot mount an effective innate immune response
Aged mice are unable to mount an effective myeloid response to sepsis.
Specimen part, Treatment, Time
View Samples