MLX siRNA knockdown in primary human hepatocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE219162 | GEO | 2023/04/21
REPOSITORIES: GEO
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Project description:This study set out to identify MLX transcriptional targets in muscle cells. C2C12 Myoblasts were virally transduced to increase MLX activity, by overexpression of the wild-type protein; and to decrease MLX activity by overexpression of a dominant negative MLX protein and by shRNA induced knockdown of MLX. Transcripts that were significantly and consistently regulated by the different modes of MLX modulation were identified. The largest proportion of these were genes encoding secreted proteins including growth factors, cytokines and extracellular proteins. We therefore conclude that MLX can regulate myokine transcripts. mRNA profiles from C2C12 muscle cells with increased and decreased MLX activity were examined.
2016-01-04 | E-GEOD-70028 | biostudies-arrayexpress
Project description:Primary human hepatocytes (PHH) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture and resistance to genetic manipulation have limited their use. Here we show that retrorsine improves human hepatocyte repopulation of chimeric mice to levels where poor donor PHH can be isolated for ex vivo cultures. Mouse-passaged (mp)PHH cultures overcome the marked donor-to-donor variability of cryopreserved PHH and remain functional for months, as demonstrated by metabolic assays and infection with hepatitis B virus and Plasmodium falciparum. mpPHH can be efficiently genetically modified in culture, mobilized and then re-cultured as spheroids or re-transplanted to create highly humanized mice carrying a genetically altered hepatocyte graft. Together, these advances provide flexible tools for studying human liver disease and evaluating hepatocyte-targeted gene therapy approaches
2019-12-02 | GSE130219 | GEO
Project description:The Myc bHLH-ZIP transcription factor is deregulated by most cancers. As a heterodimer with the bHLH-ZIP protein Max, Myc regulates target genes that contribute to metabolism and proliferation. This “Myc Network” cross-talks with the “Mlx Network” comprised of the Myc-like bHLH-ZIP proteins MondoA and ChREBP and the Max-like bHLH-ZIP protein Mlx. This “Extended Myc Network” regulates genes with both common and distinct functions. We have generated hepatocytes lacking Mlx (mlxKO) or Mlx+Myc (double KO or DKO) and quantified their abilities to replace dying hepatocytes in a murine model of Type I tyosinemia. We find that this function deteriorates as the Extended Myc Network is progressively dismantled. Genes dysregulated in mlxKO and DKO hepatocytes include those involved in translation and mitochondrial function. The Myc and Mlx Networks thus cross-talk with the latter playing a disproportionate role. mycKO and mlxKO mice also develop age-dependent non-alcoholic fatty liver disease and mlxKO and DKO mice develop extensive hepatic adenomatosis not observed in wild-type, mycKO, chrebpKO or mycKOxchrebpKO mice. In addition to demonstrating cooperation between the Myc and Mlx Networks, this study reveals the latter to be more important in maintaining metabolic and translational homeostasis, while concurrently serving as a suppressor of benign tumorigenesis.
2022-05-05 | GSE181371 | GEO
Project description:We generated mice null for MAX-like Protein X (MLX), encoded by Mlx. All male mice are sterile. We profiled testes tissue from WT versus KO mice by RNA-Seq. We performed ChIP-Seq on WT and KO testes for MLX and MAX, as well as ChIP-Seq for MLX and MAX from primary B220+ splenic B cells, and ChIP-Seq for MLX, MAX and MNT from 3T3 cell lines derived from WT and KO embryos.
2021-07-31 | GSE165820 | GEO
Project description:This study set out to identify MLX transcriptional targets in muscle cells. C2C12 Myoblasts were virally transduced to increase MLX activity, by overexpression of the wild-type protein; and to decrease MLX activity by overexpression of a dominant negative MLX protein and by shRNA induced knockdown of MLX. Transcripts that were significantly and consistently regulated by the different modes of MLX modulation were identified. The largest proportion of these were genes encoding secreted proteins including growth factors, cytokines and extracellular proteins. We therefore conclude that MLX can regulate myokine transcripts.
2016-01-04 | GSE70028 | GEO
Project description:Metabolic stress and changes in nutrient levels modulate many aspects of skeletal muscle function during aging and disease. Growth factors and cytokines secreted by skeletal muscle, known as myokines, are important signaling factors but it is largely unknown whether they modulate muscle growth and differentiation in response to nutrients. Here, we find that changes in glucose levels increase the activity of the glucose-responsive transcription factor MLX, which promotes and is necessary for myoblast fusion. MLX promotes myogenesis not via an adjustment of glucose metabolism but rather by inducing the expression of several myokines, including insulin like-growth factor-2 (IGF2), whereas RNAi and dominant-negative MLX reduce IGF2 expression and block myogenesis. This phenotype is rescued by conditioned media from control muscle cells and by recombinant IGF2, which activates the myogenic kinase Akt. Importantly, MLX null mice display decreased IGF2 induction and diminished muscle regeneration in response to injury, indicating that the myogenic function of MLX is conserved in vivo. Thus, glucose is a signaling molecule that regulates myogenesis and muscle regeneration via MLX/IGF2/Akt signaling.â??The data pproided are histome H4 acetlation data for MLX DN and MLX wt samples; 3 MLX DN H4 Ac Chip seq samples , 3 Inputs, 3 MLX WT H4 Ac samples and 3 WT inputs
2015-11-11 | E-GEOD-74678 | biostudies-arrayexpress
Project description:Metabolic stress and changes in nutrient levels modulate many aspects of skeletal muscle function during aging and disease. Growth factors and cytokines secreted by skeletal muscle, known as myokines, are important signaling factors but it is largely unknown whether they modulate muscle growth and differentiation in response to nutrients. Here, we find that changes in glucose levels increase the activity of the glucose-responsive transcription factor MLX, which promotes and is necessary for myoblast fusion. MLX promotes myogenesis not via an adjustment of glucose metabolism but rather by inducing the expression of several myokines, including insulin like-growth factor-2 (IGF2), whereas RNAi and dominant-negative MLX reduce IGF2 expression and block myogenesis. This phenotype is rescued by conditioned media from control muscle cells and by recombinant IGF2, which activates the myogenic kinase Akt. Importantly, MLX null mice display decreased IGF2 induction and diminished muscle regeneration in response to injury, indicating that the myogenic function of MLX is conserved in vivo. Thus, glucose is a signaling molecule that regulates myogenesis and muscle regeneration via MLX/IGF2/Akt signaling. The data pproided are histome H4 acetlation data for MLX DN and MLX wt samples;
2015-11-11 | GSE74678 | GEO
Project description:mRNA from primary PHH or iHCC was prepared according to the TruSeqTM RNA Sample Preparation Guide, and sequencing was performed on BGISEQ-500 (BGI, Wuhan, China).
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Project description:A systematic analysis of super-enhancers identified MLX as a potential oncogene in osteosarcoma. Knockdown of MLX impaired tumor aggressiveness in vitro and in vivo, suggesting oncogenic properties of MLX. Mechanistically, silencing of MLX downregulates SLC7A11, a key gene encoding glutamate/cystine antiporter, to attenuate the uptake of cystine and interrupt the redox balance, leading to ferroptotic cell death. Pharmacological inhibition of SLC7A11 triggered massive ferroptosis and caused impaired tumor growth, providing a promising approach for osteosarcoma treatment.
2023-08-08 | GSE220173 | GEO
Project description:To goal of this study was to determine the effects of GenX on freshly isolated primary human hepatocytes (PHH).
2022-07-21 | GSE187633 | GEO