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

Mikhail Baryshev (Coresponding Author), Nikolai Petrov, Vladimir Ryabov, Boris Popov (Coresponding Author)

Research output: Contribution to journalArticlepeer-review

Abstract

The 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 pRb into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous pRb, despite being G-418 resistant. However, the consequences of the transient production of exogenous pRb 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.

Original languageEnglish
JournalGenes and Diseases
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Adipogenic differentiation
  • DNA methyltransferase 1
  • Mesenchymal stem cells
  • MSCs
  • RB
  • Retinoblastoma susceptibility gene

Field of Science

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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