Search results for "Kruppel-Like Transcription Factors"
showing 10 items of 15 documents
Silencing of hepatic fate-conversion factors induce tumorigenesis in reprogrammed hepatic progenitor-like cells
2016
Abstract Background Several studies have reported the direct conversion of mouse fibroblasts to hepatocyte-like cells with different degrees of maturation by expression of hepatic fate-conversion factors. Methods We have used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2, Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells. Results We have generated hepatic cells with progenitor-like features (iHepL cells). iHepL cells displayed basic hepatocyte functions but failed to perform functions characteristic of mature hepatocytes such as significant Cyp450 or urea cycle activities. iHepL cells expressed multiple hepatic-specific …
Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes
2015
Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15), a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populat…
Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.
2015
The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in …
The gene encoding the transcriptional repressor BERF-1 maps to a region of conserved synteny on mouse chromosome 16 and human chromosome 3 and a rela…
1999
We have recently identified and characterized a Kruppel-like zinc finger protein (BERF-1), that functions as a repressor of β enolase gene transcription. By interspecific backcross analysis the gene encoding BERF-1 was localized 4.7 cM proximal to the <i>Mtv6</i> locus on mouse chromosome 16, and an isolated pseudogene was localized to mouse chromosome 8, about 5.3 cM distal to the D8Mit4 marker. Nucleotide sequence identity and chomosome location indicate that the gene encoding BERF-1 is the mouse homologue (<i>Zfp148</i>) of ZNF148 localized to human chromosome 3q21, a common translocation site in acute myeloid leukemia patients.
GLI3 is rarely implicated in OFD syndromes with midline abnormalities
2011
A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining ninety-three probands here. This includes nineteen probands (twelve mutations) who fulfilled clinical criteria for GCPS or PHS, forty-eight probands (sixteen mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), twenty-one probands (six mutations) with featu…
Gata4 Blocks Somatic Cell Reprogramming By Directly Repressing Nanog
2012
Abstract Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated the role of Gata4 in the reprogramming process and present evidence for a negative role of this family of transcription factors in the induction of pluripotency. Coexpression of Gata4 with Oct4, Klf4, and Sox2 with or without Myc in mouse embryonic fibroblasts greatly impaired reprogramming and endogenous Nanog expression. The lack of Nanog upregulation was associated with a blockade in the transition from the initiation phase of reprogramming to the full pluripotent state characteristic of iPS cells. Addition of Nanog …
Demethylation treatment restores hic1 expression and impairs aggressiveness of head and neck squamous cell carcinoma.
2010
Promoter hypermethylation of tumor suppressor genes is a common feature of primary cancer cells. However, at date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis are not yet been well defined. In the present study we analysed the methylation status of the gene hypermethylated in cancer-1 (hic1), a gene located on chromosome 17p13.3, a region frequently lost in HNSCC. We analysed 22 HNSCC samples and three cell lines using methylation specific PCR (MSP). We found hic1 methylated in 21 out of 22 samples and in all three cell lines. Treatment of the cell lines with the demethylating agent 5-Azacytidin (5-Aza) resulted in the demethylation…
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.
2016
During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition…
Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells
2013
Objectives: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. Study Design: �e developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral canDesign: �e developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral canesign: �e developed a vector-based siRNA expression system that can induce RN…
Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception.
2009
To study possible effects of assisted reproductive technologies (ART) on epigenetic reprogramming, we have analyzed the DNA methylation levels of differentially methylated regions (DMRs) of seven imprinted genes (H19, MEG3, LIT1, MEST, NESP55, PEG3 and SNRPN) as well as the promoter regions of the pluripotency gene NANOG and the tumor suppressor gene APC in chorionic villus samples (CVS) of 42 spontaneous miscarriages and stillbirths after ART and 29 abortions/stillbirths after spontaneous conception. We did not find an increased rate of faulty methylation patterns after ART, but significant and trend differences (ROC curve analysis, Wilcoxon test) in the methylation levels of LIT1 (P = 0.0…