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Gene expression profiling of Hif1α defective hearts in E12.5 mice

ABSTRACT: Hypoxia is an important environmental cue in heart development. Despite of extensive characterization of gain and loss of function models, there is disagreement about the impact of HIF1 signaling elimination during cardiac development. Here, we used new conditional knock out models of Hif1α in Nkx2.5 cardiac progenitors and cardiomyocytes to assess the morphological and functional consequences of HIF1α loss in the developing heart. By combining histology, electron microscopy and high-throughput genomics and proteomics, we found that deletion of Hif1α leads to impaired embryonic glycolysis without influencing cardiomyocyte proliferation and results in an increased mitochondrial number, activation of a transient amino acid response and temporal upregulation of HIF2α and ATF4 by E12.5. Hif1α mutants display normal expression of genes and proteins involved in fatty acid oxidation and do not show any sign of cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling is dispensable for heart development and reveal the metabolic flexibility of the embryonic myocardium, opening the potential application of alternative energy sources as therapeutic interventions during ischemic events.

ORGANISM(S): Mus musculus

PROVIDER: GSE164453 | GEO | 2021/01/21

REPOSITORIES: GEO

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