MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal. (22nd April 2018)

• Record Type: Journal Article
• Authors: James, Christina; Zhao, Tian Yun; Rahim, Anisa; Saxena, Parul; Muthalif, Nazreen Abdul; Uemura, Takeshi; Tsuneyoshi, Norihiro; Ong, Sheena; Igarashi, Kazuei; Lim, Chin Yan; Dunn, Norris Ray; Vardy, Leah A.
• Is Part Of: Stem cells. Volume 36:Number 8(2018)
• Page Start: 1170
• Page End: 1178
• Publication Date: 2018-04-22
• Subjects: Polyamines -- Embryonic stem cells -- miRNAs -- Self-renewal -- MINDY1; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2830
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self-renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self-renewal and that they function, in part, through promotion of high MINDY1 levels. Abstract : Polyamines promote high levels of MINDY1. MINDY1 is a deubiquitinase that promotes self-renewal likely by deubiquitinating and thus stabilizing core self-renewal factors.