Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression in zebrafish following knockdown of pitx2 or tbx5

ABSTRACT: Key regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting uncharacterized primordial functions of these septation regulators prior to the evolution of any physical boundaries between heart chambers. Data is as published in Mosimann & Panakova et al (Nature Communications, 2015) Samples for tbx5a versus pitx2ab MO comparison were collected from three independent experiments of MO-injected siblings and uninjected wildtype controls at 56hpf by morphology.

ORGANISM(S): Danio rerio

SUBMITTER: Gabriel Musso

PROVIDER: E-GEOD-70750 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease. To identify a common cellular response to primary RC that might improve mechanistic understanding and lead to targeted therapies for human RC disease, we performed collective transcriptome profiling in skeletal muscle biopsy specimens and fibroblast cell lines (FCLs) of a diverse cohort of human mitochondrial disease subjects relative to controls. Systems biology investigations of common cellular responses to primary RC disease revealed a collective pattern of transcriptional, post-transcriptional and translational dysregulation occurring in a highly tissue-specific fashion. Affymetrix Human Exon 1.0ST microarray analysis was performed on 29 skeletal muscle samples and Fibroblast cell lines from mitochondrial disease patients and age- and gender-matched controls.

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Gene expression in zebrafish following knockdown of pitx2 or tbx5

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