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Article

Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

1
Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
2
Center for Metabolic Diseases, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Robert David
Int. J. Mol. Sci. 2021, 22(15), 7813; https://doi.org/10.3390/ijms22157813
Received: 25 June 2021 / Revised: 14 July 2021 / Accepted: 21 July 2021 / Published: 22 July 2021
Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells. View Full-Text
Keywords: stem cells; proliferation; survival and cardiac repair stem cells; proliferation; survival and cardiac repair
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MDPI and ACS Style

Kraus, L.; Bryan, C.; Wagner, M.; Kino, T.; Gunchenko, M.; Jalal, W.; Khan, M.; Mohsin, S. Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation. Int. J. Mol. Sci. 2021, 22, 7813. https://doi.org/10.3390/ijms22157813

AMA Style

Kraus L, Bryan C, Wagner M, Kino T, Gunchenko M, Jalal W, Khan M, Mohsin S. Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation. International Journal of Molecular Sciences. 2021; 22(15):7813. https://doi.org/10.3390/ijms22157813

Chicago/Turabian Style

Kraus, Lindsay, Chris Bryan, Marcus Wagner, Tabito Kino, Melissa Gunchenko, Wassy Jalal, Mohsin Khan, and Sadia Mohsin. 2021. "Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation" International Journal of Molecular Sciences 22, no. 15: 7813. https://doi.org/10.3390/ijms22157813

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