Tgif1 is a transcriptional corepressor that limits TGF responsive gene expression. TGF signaling has antiproliferative effects in several cell types, generally resulting in a G1 arrest. Mouse embryo fibroblasts (MEFs) are primary cells with limited life-span, that senesce after several passages in culture.
Premature senescence and increased TGFβ signaling in the absence of Tgif1.
Specimen part
View SamplesPhotoreceptor damage in adult mammals results in permanent cell loss and glial scarring in the retina. In contrast, adult zebrafish can regenerate photoreceptors following injury. By using a stable transgenic line in which GFP is driven by the cis-regulatory sequences of a glial specific marker gfap, Tg(gfap:GFP)mi2002, previous studies showed that Mller glia, the radial glial cells in the retina, proliferate after photoreceptor loss and give rise to neuronal progenitors that eventually differentiate into regenerated photoreceptors. To identify the molecular mechanisms that initiate this regenerative response, Mller glia were isolated from Tg(gfap:GFP)mi2002 fish during the early stages of regeneration after light lesion and gene expression profiles were generated by microarray analyses.
Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish.
No sample metadata fields
View SamplesA soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sex, Specimen part
View SamplesThe goal of the project was to isolate single miRNA-expressing cells labelled by GFP reporter genes under the control of endogenous miRNA promoters and analyze expression levels of miRNA target genes in these cells. GFP-positive miRNA-expressing cells and GFP-negative cells from the rest of the embryos were purified at the same developmental stage to the cellular resolution using fluorescent activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
No sample metadata fields
View SamplesThe study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity.
Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.
No sample metadata fields
View SamplesTo guarantee blood supply throughout adult life hematopoietic stem cells (HSCs) need to carefully balance between self-renewing cell divisions and quiescence. Identification of genes controlling HSC self-renewal is of utmost importance given that HSCs are the only stem cells with broad clinical applications. Transcription factor PU.1 is one of the major regulators of myeloid and lymphoid development. Recent reports suggest that PU.1 mediates its functions via gradual expression level changes rather than binary on/off states. So far, this has not been considered in any study of HSCs and thus, PU.1s role in HSC function has remained largely unclear. Here we demonstrate using hypomorphic mice with an engineered disruption of an autoregulatory feedback loop that decreased PU.1 levels resulted in loss of key HSC functions, all of which could be fully rescued by restoration of proper PU.1 levels via a human PU.1 transgene. Mechanistically, we found excessive HSC cell divisions and altered expression of cell cycle regulators whose promoter regions were bound by PU.1 in normal HSCs. Adequate PU.1 levels were maintained by a mechanism of direct autoregulation restricted to HSCs through a physical interaction of a -14kb enhancer with the proximal promoter. Our findings identify PU.1 as novel regulator controling the switch between cell division and quiescence in order to prevent exhaustion of HSCs. Given that even moderate level changes greatly impact stem cell function, our data suggest important therapeutic implications for leukemic patients with reduced PU.1 levels. Moreover, we provide first proof, that autoregulation of a transcription factor, PU.1, has a crucial function in vivo. We anticipate that our concept of how autoregulation forms an active chromosomal conformation will impact future research on transcription factor networks regulating stem cell fate.
Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The impact of microRNAs on protein output.
No sample metadata fields
View SamplesThis array analysis is to study the regulation of target messages expression in in vitro cultured murine neutrophils versus miR-223 null neutrophils. Culture media was SILAC-IMDM for MS analysis.
The impact of microRNAs on protein output.
No sample metadata fields
View SamplesThis array analysis is to study the regulation of target messages expression in murine neutrophils versus miR-223 null neutrophils.
The impact of microRNAs on protein output.
No sample metadata fields
View SamplesThe transcription factor Nkx2.5 is required for specification of pharyngeal arch second heart field (SHF) progenitors that contribute to outflow tract (OFT) and right ventricle (RV) formation. Multiple sets of microarray data were analyzed to identify genes that are candidate targets of Nkx2.5 in the second heart field. These sets are: 1) publicly available data for cardiothoracic tissue from E9.5 Nkx2.5 wild-type, heterozygous and homozygous embryos; 2) an analysis of mouse E10.5 pharyngeal arch tissue; 3) an analysis of mouse E12.5 heart tissue; and 4) a temporal analysis of the cardiogenic cell line P19CL6. This combined analysis identified 11 genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF-containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5 expression.
Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Specimen part, Cell line
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