Pwp1 Is Required for the Differentiation Potential of Mouse Embryonic Stem Cells Through Regulating Stat3 Signaling. (March 2015)

• Record Type: Journal Article
• Authors: Shen, Junwei; Jia, Wenwen; Yu, Yangyang; Chen, Jie; Cao, Xinkai; Du, Yanhua; Zhang, Xiaobai; Zhu, Songcheng; Chen, Wen; Xi, Jiajie; Wei, Tingyi; Wang, Guiying; Yuan, Detian; Duan, Tao; Jiang, Cizhong; Kang, Jiuhong
• Is Part Of: Stem cells. Volume 33:Number 3(2015:Mar.)
• Page Start: 661
• Page End: 673
• Publication Date: 2015-03
• 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.1876
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Leukemia inhibitory factor/<italic>Stat3</italic> signaling is critical for maintaining the self‐renewal and differentiation potential of mouse embryonic stem cells (mESCs). However, the upstream effectors of this pathway have not been clearly defined. Here, we show that periodic tryptophan protein 1 (<italic>Pwp1</italic>), a WD‐40 repeat‐containing protein associated with histone H4 modification, is required for the exit of mESCs from the pluripotent state into all lineages. Knockdown (KD) of <italic>Pwp1</italic> does not affect mESC proliferation, self‐renewal, or apoptosis. However, KD of <italic>Pwp1</italic> impairs the differentiation potential of mESCs both in vitro and in vivo. PWP1 chromatin immunoprecipitation‐seq results revealed that the PWP1‐occupied regions were marked with significant levels of H4K20me3. Moreover, <italic>Pwp1</italic> binds to sites in the upstream region of <italic>Stat3</italic>. KD of <italic>Pwp1</italic> decreases the level of H4K20me3 in the upstream region of <italic>Stat3</italic> gene and upregulates the expression of <italic>Stat3</italic>. Furthermore, <italic>Pwp1</italic> KD mESCs recover their differentiation potential through suppressing the expression of <italic>Stat3</italic> or inhibiting the tyrosine phosphorylation of STAT3. Together, our results suggest that <italic>Pwp1</italic> plays important roles in the differentiation potential of mESCs. S<sc>tem</sc> C<sc>ells</sc><italic>2015;33:661–673</italic></p> </abstract>