From fa3caba85db2303653f58364f82048a95e8a7df5 Mon Sep 17 00:00:00 2001 From: ckuenne Date: Fri, 14 Apr 2023 16:13:28 +0200 Subject: [PATCH] Update README.md --- README.md | 4 ---- 1 file changed, 4 deletions(-) diff --git a/README.md b/README.md index efc888f..292621a 100644 --- a/README.md +++ b/README.md @@ -1,9 +1,5 @@ # Li_et_al_2023_heart_regeneration - !! **TODO** !! replace zenodo link below - -[![DOI](https://zenodo.org/badge/552852940.svg)](https://zenodo.org/badge/latestdoi/552852940) - ABSTRACT: Postnatal maturation of cardiomyocytes is characterized by a metabolic switch from glycolysis to fatty acid oxidation (FAO), chromatin reconfiguration, and exit from cell cycle, instating a barrier for adult heart regeneration. To explore whether metabolic reprogramming overcomes this barrier and enables heart regeneration, we abrogate FAO in cardiomyocytes by inactivation of Cpt1b. We find that disablement of FAO in cardiomyocytes improves resistance to hypoxia and stimulates cardiomyocyte proliferation, allowing heart regeneration after ischemia/reperfusion injury. Metabolic studies reveal profound changes in energy metabolism and accumulation of α-ketoglutarate in Cpt1b-mutant cardiomyocytes, leading to activation of the α-ketoglutarate-dependent lysine demethylase KDM5. Activated KDM5 demethylates broad H3K4me3 domains in genes driving cardiomyocyte maturation, lowering transcription and shifting cardiomyocytes into a less mature state, thereby promoting proliferation. We conclude that metabolic maturation shapes the epigenetic landscape of cardiomyocytes, creating a roadblock for further cell divisions. Reversal of this process allows repair of damaged hearts.