C1EIP Functions as an Activator of ENO1 to Promote Chicken PGCs Formation via Inhibition of the Notch Signaling Pathway

Kai Jin; Dong Li; Jing Jin; Jiuzhou Song; Yani Zhang; Guobing Chang; Guohong Chen; Bichun Li

doi:10.3389/fgene.2020.00751

C1EIP Functions as an Activator of ENO1 to Promote Chicken PGCs Formation via Inhibition of the Notch Signaling Pathway

Front Genet. 2020 Jul 24:11:751. doi: 10.3389/fgene.2020.00751. eCollection 2020.

Authors

Kai Jin^{1

2

3}, Dong Li⁴, Jing Jin^{1

2

3}, Jiuzhou Song⁵, Yani Zhang^{1

2

3}, Guobing Chang^{1

2

3}, Guohong Chen^{1

2

3}, Bichun Li^{1

2

3}

Affiliations

¹ Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
² Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, China.
³ Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, China.
⁴ Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China.
⁵ Animal & Avian Sciences, University of Maryland, College Park, College Park, MD, United States.

Abstract

The production of germ cells, especially primordial germ cells (PGCs), is important for avian stem cells and reproduction biology. However, key factors involved in the regulation of PGCs remain unknown. Here, we report a PGC-related marker gene: C1EIP (Chromosome 1 Expression in PGCs), whose activation and expression are regulated by the transcription factor STAT3 (signal transducer and activator of transcription 3), histone acetylation, and promoter methylation. C1EIP regulates PGCs formation by mediating the expression of PGC-associated genes, such as CVH (Chicken Vasa Homologous) and CKIT (Chicken KIT proto-oncogene). C1EIP knockdown during embryonic development reduces PGC generation efficiency both in vitro and in ovo. Conversely, C1EIP overexpression increases the formation efficiency of PGCs. C1EIP encodes a cytoplasmic protein that interacts with ENO1 (Enolase 1) in the cytoplasm, inhibits the Notch signaling pathway, and positively regulates PGC generation. Collectively, our findings demonstrate C1EIP as a novel gene involved in PGC formation, which regulates genes involved in embryonic stem cell differentiation through interaction with ENO1 and subsequent inhibition of the Notch signaling pathway by the impression of Myc (MYC proto-oncogene).

Keywords: C1EIP; ENO1; Notch signal; chicken PGCs; germ cell differentiation.