Summary of Study ST002242

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.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST002242
Study TitleHypoxia promotes osteogenesis via regulating the acetyl-CoA-mediated mito-nuclear communication.
Study SummaryBone-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.
CECAD Research Center
Last NameYang
First NameMing
AddressJoseph-Stelzmann-Straße 26, Köln, Koeln, 50931, Germany
Submit Date2022-08-01
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-08-17
Release Version1
Ming Yang Ming Yang application/zip

Select appropriate tab below to view additional metadata details:


Collection ID:CO002321
Collection Summary:To isolate mitochondrial and cytosolic cellular fractions we followed a previously published rapid subcellular fractionation method (Lee et al., 2019). Briefly, on the day of the experiment, cells were washed twice with ice-cold PBS and scraped from the flasks with 2 ml PBS. 1:4 of cells was transferred to a tube and served as the whole cell lysate (WCL). After a brief centrifugation step (10,000 g, 3 minutes, 4 °C), supernatant was removed and 300 ul of metabolite extraction solution (50%MetOH:30%acetonitrile:20% ultrapure water) was added to samples. Samples were incubated with the extraction buffer for 20 minutes in a dry-ice MetOH water-bath and were then subjected to metabolite extraction. The rest 3:4 of cells was subjected to digitonin-based cellular fractionation. More precisely, after a brief centrifugation step (10,000 g, 10 sec, 4 °C), supernatant was removed and the pellet was resuspended in 1 ml of ice-cold digitonin-PBS buffer (1mg/ml). Following quick centrifugation (10,000 g, 10 sec, 4 °C), supernatant and pellet were collected as the cytosolic and mitochondrial fractions, respectively. 4 ml of 50%MetOH:30%acetonitrile was added in the cytosolic fractions to extract metabolites. Samples were incubated for 20 minutes in a dry-ice MetOH water-bath and were then subjected to metabolite extraction. The mitochondrial fraction was resuspended in 100 ul metabolite extraction solution and incubated for 20 minutes in a dry-ice MetOH water-bath and were then subjected to metabolite extraction.
Sample Type:Cultured cells