Summary of project PR001431

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001431. The data can be accessed directly via it's Project DOI: 10.21228/M8RD8W This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001431
Project DOI:doi: 10.21228/M8RD8W
Project Title:Hypoxia promotes osteogenesis via regulating the acetyl-CoA-mediated mito-nuclear communication.
Project Summary:Bone-mesenchymal stem cells (MSCs) reside in a hypoxic niche that maintains their differentiation potential. Although the role of hypoxia (low oxygen concentration) in the regulation of stem cell function has been previously reported, with normoxia (high oxygen concentration) leading to impaired osteogenesis, the molecular events triggering changes in stem cell fate decisions in response to high oxygen remain elusive. Here, we study the impact of normoxia on the mito-nuclear communication with regards to stem cell differentiation. We show that normoxia-cultured MSCs undergo profound transcriptional alterations which cause irreversible osteogenesis defects. Mechanistically, high oxygen promotes chromatin compaction and histone hypo-acetylation, particularly on promoters and enhancers of osteogenic genes. Although normoxia induces metabolic rewiring resulting in high acetyl-CoA levels, histone hypo-acetylation occurs due to trapping of acetyl-CoA inside mitochondria, owing to lower CiC activity. Strikingly, restoring the cytosolic acetyl-CoA pool remodels the chromatin landscape and rescues the osteogenic defects. Collectively, our results demonstrate that the metabolism-chromatin-osteogenesis axis is heavily perturbed in response to high oxygen and identify CiC as a novel, oxygen-sensitive regulator of the MSC function.
Institute:CECAD Research Center
Last Name:Yang
First Name:Ming
Address:Joseph-Stelzmann-Straße 26, Köln, Koeln, 50931, Germany

Summary of all studies in project PR001431

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002242 Hypoxia promotes osteogenesis via regulating the acetyl-CoA-mediated mito-nuclear communication. Mus musculus CECAD Research Center MS 2022-08-17 1 24 Uploaded data (4.6G)*