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DNA methylation analysis identifies key transcription factors involved in mesenchymal stem cell osteogenic differentiation

Overview of attention for article published in Biological Research, March 2023
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

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Title
DNA methylation analysis identifies key transcription factors involved in mesenchymal stem cell osteogenic differentiation
Published in
Biological Research, March 2023
DOI 10.1186/s40659-023-00417-6
Pubmed ID
Authors

Rodolfo Gómez, Matt J. Barter, Ana Alonso-Pérez, Andrew J. Skelton, Carole Proctor, Gabriel Herrero-Beaumont, David A. Young

Abstract

Knowledge about regulating transcription factors (TFs) for osteoblastogenesis from mesenchymal stem cells (MSCs) is limited. Therefore, we investigated the relationship between genomic regions subject to DNA-methylation changes during osteoblastogenesis and the TFs known to directly interact with these regulatory regions. The genome-wide DNA-methylation signature of MSCs differentiated to osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. During adipogenesis no CpGs passed our test for significant methylation changes. Oppositely, during osteoblastogenesis we identified 2462 differently significantly methylated CpGs (adj. p < 0.05). These resided outside of CpGs islands and were significantly enriched in enhancer regions. We confirmed the correlation between DNA-methylation and gene expression. Accordingly, we developed a bioinformatic tool to analyse differentially methylated regions and the TFs interacting with them. By overlaying our osteoblastogenesis differentially methylated regions with ENCODE TF ChIP-seq data we obtained a set of candidate TFs associated to DNA-methylation changes. Among them, ZEB1 TF was highly related with DNA-methylation. Using RNA interference, we confirmed that ZEB1, and ZEB2, played a key role in adipogenesis and osteoblastogenesis processes. For clinical relevance, ZEB1 mRNA expression in human bone samples was evaluated. This expression positively correlated with weight, body mass index, and PPARγ expression. In this work we describe an osteoblastogenesis-associated DNA-methylation profile and, using these data, validate a novel computational tool to identify key TFs associated to age-related disease processes. By means of this tool we identified and confirmed ZEB TFs as mediators involved in the MSCs differentiation to osteoblasts and adipocytes, and obesity-related bone adiposity.

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The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 2 33%
Student > Bachelor 1 17%
Student > Doctoral Student 1 17%
Student > Ph. D. Student 1 17%
Researcher 1 17%
Other 0 0%
Readers by discipline Count As %
Medicine and Dentistry 3 50%
Biochemistry, Genetics and Molecular Biology 2 33%
Unknown 1 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2023.
All research outputs
#6,246,553
of 25,401,784 outputs
Outputs from Biological Research
#65
of 642 outputs
Outputs of similar age
#108,278
of 423,724 outputs
Outputs of similar age from Biological Research
#4
of 15 outputs
Altmetric has tracked 25,401,784 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 642 research outputs from this source. They receive a mean Attention Score of 3.3. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 423,724 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.