Skeletal muscle regeneration is a highly dynamics process. The study aims at investigating gene expression by endothelial cells and satellite/myogenic cells during this process, in mouse, after a toxic injury
Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages.
Specimen part, Time
View SamplesSomatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) and dark zone (DZ) germinal center (GC) B cells were compared in immunized AIDcre/- IgH-96K/+ R26-LSL-YFP mice.
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Specimen part, Cell line, Subject
View SamplesSomatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) germinal center (GC) B cells that were Nurr77-GFP+ or Nurr77-GFP- were compared in immunized AIDcre/- IgH-96K/+ Nurr77-GFP mice.
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Specimen part, Cell line, Subject
View SamplesThe germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles. Overall design: To determine whether GC B cells receiving high levels of T cell help show a specific change in gene expression, we compared DZ cells in the G1 phase of the cell cycle from aDEC-OVA and control aDEC-CS treated GCs using a fluorescent ubiquitination-based cell cycle indicator (Fucci-tg). RNA sequencing revealed that T cell-mediated selection produced an increase in gene expression programs associated with the cell cycle, metabolism, including the metabolism of nucleotides, and genes downstream of c-Myc and the E2F transcription factors.
HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3.
Cell line, Time
View SamplesWe measured the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic - and -cell lines.
Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesExperiment 1 - miR-155 and miR-199 Phenotype
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesExperiment 2 - MiRNA mimics have a length and passenger strand specific effect
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Cell line
View SamplesHox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Overall design: RNA-seq from mouse E12.5 digits cells and mouse E15.5 genital tubercle cells.
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci.
No sample metadata fields
View Samples