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Polycomb protein BMI1 regulates osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells downstream of GSK3

Polycomb proteins such as the B lymphoma Mo-MLV insertion region 1 homolog (BMI1) are essential chromatin factors for the self-renewal and differentiation of embryonic and adult stem cells. BMI1 also plays a critical role in osteogenesis as Bmi1-deficient mice display a skeletal phenotype caused by...

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Bibliographic Details
Main Authors: Becker, Matthias (Author) , Bieback, Karen (Author) , Ho, Anthony Dick (Author)
Format: Article (Journal)
Language:English
Published: April 21, 2016
In: Stem Cells and Development
Year: 2016, Volume: 25, Issue: 12, Pages: 922-933
ISSN:1557-8534
DOI:10.1089/scd.2015.0277
Online Access:Verlag, Volltext: http://dx.doi.org/10.1089/scd.2015.0277
Verlag, Volltext: https://www.liebertpub.com/doi/abs/10.1089/scd.2015.0277
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Author Notes:Matthias Becker, Tamara Potapenko, Andrea Niklaus, Karen Bieback, Anthony D. Ho, and Albrecht M. Müller
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Summary:Polycomb proteins such as the B lymphoma Mo-MLV insertion region 1 homolog (BMI1) are essential chromatin factors for the self-renewal and differentiation of embryonic and adult stem cells. BMI1 also plays a critical role in osteogenesis as Bmi1-deficient mice display a skeletal phenotype caused by the exhaustion of the mesenchymal stem cell pool. In this study, we have studied the role of BMI1 in the osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). BMI1 protein, but not RNA levels, increases during in vitro osteogenic differentiation of hASCs. Overexpression of BMI1 leads to an osteogenic priming of hASCs under nondifferentiating conditions and enhanced osteogenesis upon differentiation, along with increased BMP2 and WNT11 expressions. Conversely, knockdown of BMI1 expression reduces osteogenic differentiation. Furthermore, our studies indicate that during osteogenic differentiation of hASCs, BMI1 is a downstream target of GSK3 signaling. BMI1, therefore, acts as a pro-osteogenic differentiation factor in hASCs and hence it is a promising target for active modulation of hASC-derived osteogenesis.
Item Description:Gesehen am 21.12.2018
Physical Description:Online Resource
ISSN:1557-8534
DOI:10.1089/scd.2015.0277

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