Transient expression of inactive RB in mesenchymal stem cells impairs their adipogenic potential and is associated with hypermethylation of the PPARγ2 promoter

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dc.contributor.authorBaryshev, Mikhail
dc.contributor.authorPetrov, Nikolai
dc.contributor.authorRyabov, Vladimir
dc.contributor.authorPopov, Boris
dc.contributor.institutionInstitute of Microbiology and Virology
dc.date.accessioned2022-01-27T11:30:01Z
dc.date.available2022-01-27T11:30:01Z
dc.date.issued2022-01
dc.descriptionFunding Information: We many thanks Dr. P. Hamel and Dr. R. Phillips, The Hospital for Sick Children, Toronto, Canada for generously presented plasmids. This work was supported by an internal grant from the Institute of Cytology RAS and in part by an internal grant from Rīga Stradiņš University under a cooperation agreement. Publisher Copyright: © 2021 Chongqing Medical University
dc.description.abstractThe retinoblastoma gene product (pRb) is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation. We found that twelve weeks after transfection of the exogenous active (ΔB/X and Δр34) or inactive (ΔS/N) forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB, despite being G-418 resistant. However, the consequences of the transient production of exogenous RB had different effects on the cell fate. The ΔB/X and Δр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation (AD). On the contrary, the ΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2. Additionally, the PPARγ2 promoter in undifferentiated ΔS/N cells was hypermethylated, but all except −60 position CpG became mostly demethylated after cells exposure to AD. We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis, production of active exogenous RBs results in an AD-promoting epigenetic state. These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.en
dc.description.statusPeer reviewed
dc.format.extent11
dc.format.extent2113886
dc.identifier.citationBaryshev, M, Petrov, N, Ryabov, V & Popov, B 2022, 'Transient expression of inactive RB in mesenchymal stem cells impairs their adipogenic potential and is associated with hypermethylation of the PPARγ2 promoter', Genes and Diseases, vol. 9, no. 1, pp. 165-175. https://doi.org/10.1016/j.gendis.2020.11.001
dc.identifier.doi10.1016/j.gendis.2020.11.001
dc.identifier.issn2352-3042
dc.identifier.otherMendeley: b3558e1b-8239-3812-aac9-b752d760e6e7
dc.identifier.otherunpaywall: 10.1016/j.gendis.2020.11.001
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/7331
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85096837787&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofGenes and Diseases
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAdipogenic differentiation
dc.subjectDNA methyltransferase 1
dc.subjectMesenchymal stem cells
dc.subjectMSCs
dc.subjectRB
dc.subjectRetinoblastoma susceptibility gene
dc.subject1.6 Biological sciences
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectGenetics(clinical)
dc.subjectCell Biology
dc.titleTransient expression of inactive RB in mesenchymal stem cells impairs their adipogenic potential and is associated with hypermethylation of the PPARγ2 promoteren
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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