The development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Specimen part, Cell line, Subject
View SamplesThe global gene expression profiles of human umbilical cord blood and adult bone marrow CD34+CD33-CD38-Rho(lo)c-kit+ cells, enriched for hematopoietic stem/progenitor cells (HSC) with CD34+CD33-CD38-Rho(hi) cells, enriched in committed hematopoietic progenitor cells (HPC), were compared to identify candidate regulators of HSC self-renewal versus differentiation fate decisions.
Functional analysis of human hematopoietic stem cell gene expression using zebrafish.
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View SamplesMicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Specimen part, Disease, Treatment
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesWe investigate the role of Snf2l in ovaries by characterizing a mouse bearing an inactivating deletion on the ATPase domain of Snf2l (Ex6DEL). Snf2l mutant mice produce significantly fewer eggs than control mice when superovulated. Thus, gonadotropin stimulation leads to a significant deficit in secondary follicles and an increase in abnormal antral follicles. We profiled the expression of granulosa cells from Snf2l WT and Ex6DEL mice treated with pregnant mares' serum gonadotropin followed by human chorionic gonadotropin
The imitation switch ATPase Snf2l is required for superovulation and regulates Fgl2 in differentiating mouse granulosa cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of the cortical neurons that mediate antidepressant responses.
Specimen part, Treatment
View SamplesMicroarrays were used to analyze differential gene expression and to help determine the efficacy of Iressa (gefitinib), a tyrosine kinase inhibitor, on endometrial cancer cells.
EGFR isoforms and gene regulation in human endometrial cancer cells.
Specimen part, Cell line
View SamplesNine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours.
Effects of 10 cigarette smoke condensates on primary human airway epithelial cells by comparative gene and cytokine expression studies.
Specimen part
View SamplesMolecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment.
Identification of the cortical neurons that mediate antidepressant responses.
Specimen part, Treatment
View SamplesMolecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment.
Identification of the cortical neurons that mediate antidepressant responses.
Specimen part, Treatment
View Samples