Regulation of L‐Threonine Dehydrogenase in Somatic Cell Reprogramming123. (24th April 2013)

• Record Type: Journal Article
• Authors: Han, Chuanchun; Gu, Hao; Wang, Jiaxu; Lu, Weiguang; Mei, Yide; Wu, Mian
• Is Part Of: Stem cells. Volume 31:Number 5(2013:May)
• Page Start: 953
• Page End: 965
• Publication Date: 2013-04-24
• Subjects: 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.1335
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Increasing evidence suggests that metabolic remodeling plays an important role in the regulation of somatic cell reprogramming. Threonine catabolism mediated by <sc>L</sc>‐threonine dehydrogenase (TDH) has been recognized as a specific metabolic trait of mouse embryonic stem cells. However, it remains unknown whether TDH‐mediated threonine catabolism could regulate reprogramming. Here, we report TDH as a novel regulator of somatic cell reprogramming. Knockdown of TDH inhibits, whereas induction of TDH enhances reprogramming efficiency. Moreover, microRNA‐9 post‐transcriptionally regulates the expression of TDH and thereby inhibits reprogramming efficiency. Furthermore, protein arginine methyltransferase (PRMT5) interacts with TDH and mediates its post‐translational arginine methylation. PRMT5 appears to regulate TDH enzyme activity through both methyltransferase‐dependent and ‐independent mechanisms. Functionally, TDH‐facilitated reprogramming efficiency is further enhanced by PRMT5. These results suggest that TDH‐mediated threonine catabolism controls somatic cell reprogramming and indicate the importance of post‐transcriptional and post‐translational regulation of TDH. S<sc>TEM</sc> C<sc>ELLS</sc> 2013;31:953–965</p> </abstract>