Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration.
Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.
Specimen part, Time
View SamplesWe have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311
Personal omics profiling reveals dynamic molecular and medical phenotypes.
Specimen part, Disease, Subject
View SamplesTranscription factors that regulate quiescence, proliferation, and homing of lymphocytes are critical for effective immune system function. In the present study, we demonstrated that the transcription factor ELF4 directly activates the tumor suppressor KLF4 downstream of T cell receptor (TCR) signaling to induce cell cycle arrest in nave CD8+ T cells. Elf4- and Klf4-deficient mice accumulated CD8+CD44hi T cells during steady-state conditions and generated more memory T cells after immunization. The homeostatic expansion of CD8+CD44hi T cells in Elf4-null mice resulted in a redistribution of cells to non-lymphoid tissue due to reduced expression of the transcription factor KLF2, and the surface proteins CCR7 and CD62L. This work describes the combinatorial role of lymphocyte-intrinsic factors in the control of T cell homeostasis, activation and homing.
Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2.
Specimen part
View SamplesUtilizing glycerol and cardiotoxin (CTX) injections in the tibialis anterior muscles of M. musculus provides models of skeletal muscle damages followed by skeletal muscle regeneration. In particular, glycerol-induced muscle regeneration is known to be associated with ectopic adipogenesis. We characterized genome-wide expression profiles of tibialis anterior muscles from wild-type mice injured by either glycerol or CTX injection. Our goal was to detect gene expression changes during the time course of glycerol-induced and CTX-induced muscle regeneration models, that can lead to ectopic adipocyte accumulation.
Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.
Sex, Age, Specimen part
View SamplesFollowing the identification of a critical time window of Blood Brain Barrier formation in the mouse embryo, we aimed to identify genes important for barriergenesis. To this end, we isolated cortical and lung E13.5 endothelial cells and compared expression between the two populations.
Mfsd2a is critical for the formation and function of the blood-brain barrier.
Specimen part
View SamplesBeyond the DNA sequence difference between humans and closely related apes, there are large differences in the environments that these species experience. One prominent example for this is diet. The human diet diverges from those of other primates in various aspects, such as having a high calorie and protein content, as well as being cooked. Here, we used a laboratory mouse model to identify gene expression differences related to dietary differences.
Human and chimpanzee gene expression differences replicated in mice fed different diets.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration.
Age, Specimen part
View SamplesNormal brain function critically depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. The fidelity of neuronal specification is contingent upon the robustness of the transcriptional program that supports the neuron type-specific patterns of gene expression. Changes in neuron type-specific gene expression are commonly associated with neurodegenerative disorders including Huntingtons and Alzheimers disease. The neuronal specification is driven by gene expression programs that are established during early stages of neuronal development and remain in place in the adult brain. Here we show that the Polycomb repressive complex 2 (PRC2), which supports neuron specification during early differentiation, contributes to the suppression of the transcription program that can be detrimental for the adult neuron function. We show that PRC2 deficiency in adult striatal neurons and in cerebellar Purkinje cells impairs the maintenance of neuron-type specific gene expression. The deficiency in PRC2 has a direct impact on a selected group of genes that is dominated by self-regulating transcription factors normally suppressed in these neurons. The age-dependent progressive transcriptional changes in PRC2-deficient neurons are associated with impaired neuronal function and survival and lead to the development of fatal neurodegenerative disorders in mice.
Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration.
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View SamplesIn development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution.
Transcriptional neoteny in the human brain.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
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