Pwp1 is required for the differentiation potential of mouse embryonic stem cells through regulating Stat3 signaling.

Stem Cells. 2015 Mar;33(3):661-73. doi:10.1002/stem.1876

Junwei Shen ¹ , Wenwen Jia , Yangyang Yu , Jie Chen , Xinkai Cao ,

Junwei Shen ¹ , Wenwen Jia , Yangyang Yu , Jie Chen , Xinkai Cao , Yanhua Du , Xiaobai Zhang , Songcheng Zhu , Wen Chen , Jiajie Xi , Tingyi Wei , Guiying Wang , Detian Yuan , Tao Duan , Cizhong Jiang , Jiuhong Kang

+ et al

Author information

¹ Shanghai Key Laboratory of Signaling and Disease Research, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.

摘要

Leukemia inhibitory factor/Stat3 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 (Pwp1), 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 Pwp1 does not affect mESC proliferation, self-renewal, or apoptosis. However, KD of Pwp1 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, Pwp1 binds to sites in the upstream region of Stat3. KD of Pwp1 decreases the level of H4K20me3 in the upstream region of Stat3 gene and upregulates the expression of Stat3. Furthermore, Pwp1 KD mESCs recover their differentiation potential through suppressing the expression of Stat3 or inhibiting the tyrosine phosphorylation of Together, our results suggest that Pwp1 plays important roles in the differentiation potential of mESCs.

KEYWORDS: Differentiation potential, Embryonic stem cells, Pwp1, Stat3

基因

Pwp1, Pou5f1, Sox2, Stat3, Suv420h2, Nanog

原始数据

保存测序数据

Sample name	Organism	Experiment title	Sample type	Library instrument	Attributes
Sample name	Organism	Experiment title	Sample type	Library instrument	antibody	antibody catalog number	antibody manufacturer	cell type	development stage	source name
Input DNA	Mus musculus	GSM1436144: Input DNA; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina HiSeq 2000	none (input)			mESCs	E14	mouse embryonic stem cells
Pwp1_ChIPSeq	Mus musculus	GSM1436143: Pwp1_ChIPSeq; Mus musculus; ChIP-Seq	ChIP-Seq	Illumina HiSeq 2000	anti-Pwp1	sc-107983	Santa Cruz	mESCs	E14	mouse embryonic stem cells