Open AccessMINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self‐Renewal
Author(s) -
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.
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2830
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , stem cell , spermidine , putrescine , polyamine , spermine , cellular differentiation , neural stem cell , biochemistry , gene , enzyme
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. S tem C ells 2018;36:1170–1178