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

作　　者：Mikhail Baryshev Nikolai Petrov Vladimir Ryabov Boris Popov 

机构地区：[1]Institute of Cytology Russian Academy of Sciences,St.Petersburg,4,Tikhoretsky Av.,194064,St.Petersburg,Russia [2]Institute of Microbiology and Virology,Riga Stradins University,Ratsupites 5,LV-1067,Riga,Latvia [3]Developmental Therapeutics Branch,National Cancer Institute,National Institutes of Health,Bethesda,Maryland 20892,USA

出　　处：《Genes & Diseases》2022年第1期165-175,共11页基因与疾病（英文）

摘　　要：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 andΔр34)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.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/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 undifferentiatedΔS/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.

关 键 词：Adipogenic differentiation DNA methyltransferase 1 Mesenchymal stem cells MSCS RB Retinoblastoma susceptibility gene 

分 类 号：R739.7[医药卫生—肿瘤]