Lim_2020_Int.J.Mol.Sci_21_8983

Reference

Title : Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation - Lim_2020_Int.J.Mol.Sci_21_8983
Author(s) : Lim S , Shparberg RA , Coorssen JR , O'Connor MD
Ref : Int J Mol Sci , 21 : , 2020
Abstract :

Retinoblastoma binding protein 9 (RBBP9) is required for maintaining the expression of both pluripotency and cell cycle genes in human pluripotent stem cells (hPSCs). An siRNA-based study from our group showed it does so by influencing cell cycle progression through the RB/E2F pathway. In non-pluripotent cells, RBBP9 is also known to have serine hydrolase (SH) activity, acting on currently undefined target proteins. The role of RBBP9 SH activity in hPSCs, and during normal development, is currently unknown. To begin assessing whether RBBP9 SH activity might contribute to hPSC maintenance, hPSCs were treated with ML114-a selective chemical inhibitor of RBBP9 SH activity. Stem cells treated with ML114 showed significantly reduced population growth rate, colony size and progression through the cell cycle, with no observable change in cell morphology or decrease in pluripotency antigen expression-suggesting no initiation of hPSC differentiation. Consistent with this, hPSCs treated with ML114 retained the capacity for tri-lineage differentiation, as seen through teratoma formation. Subsequent microarray and Western blot analyses of ML114-treated hPSCs suggest the nuclear transcription factor Y subunit A (NFYA) may be a candidate effector of RBBP9 SH activity in hPSCs. These data support a role for RBBP9 in regulating hPSC proliferation independent of differentiation, whereby inhibition of RBBP9 SH activity de-couples decreased hPSC proliferation from initiation of differentiation.

PubMedSearch : Lim_2020_Int.J.Mol.Sci_21_8983
PubMedID: 33256189
Gene_locus related to this paper: human-RBBP9

Related information

Inhibitor ML114
Gene_locus human-RBBP9
Family Hydrolase_RBBP9_YdeN

Citations formats

Lim S, Shparberg RA, Coorssen JR, O'Connor MD (2020)
Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation
Int J Mol Sci 21 :

Lim S, Shparberg RA, Coorssen JR, O'Connor MD (2020)
Int J Mol Sci 21 :