본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Stem cell reports v.10 no.2, 2018년, pp.524 - 537   SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase + Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia

Kuo, Yung-Che    (Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Au, Heng-Kien    (Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Hsu, Jue-Liang    (Department of Biological Science and Technology, National Pingtung University of Science and Technology, 91201 Pingtung, Taiwan   ); Wang, Hsiao-Feng    (Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Lee, Chiung-Ju    (Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Peng, Syue-Wei    (Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Lai, Ssu-Chuan    (Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan   ); Wu, Yu-Chih    (Center f  ); Ho, Hong-Nerng   Huang, Yen-Hua  
  • 초록  

    Summary Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R), and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation) and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis. Highlights • Hypoxia regulated AP + GSC self-renewal and cell migration via IGF-1R and CXCR4 • Hypoxia increased IGF1/IGF-1R and SDF-1/CXCR4 to promote AP + GSC migration • Crosstalk of IGF-1/IGF-1R and SDF-1/CXCR4 signaling in AP + GSCs under hypoxia • Inhibition of IGF-1R phosphorylation suppressed hypoxia-induced cell migration In this article, Huang and colleagues demonstrate that niche hypoxia promotes symmetric self-renewal proliferation and migration of PGC-like CD49f + AP + GSCs through IGF-IR regulation. Using a serum-free culture system, the crosstalk between IGF-1R and CXCR4 signaling was discovered. This work demonstrated that embryonic hypoxia synergistically cooperated with IGF-1R signaling to regulate the symmetric self-renewal and migration of PGC-like GSCs through a HIF-2α–OCT4/CXCR4 loop.


  • 주제어

    hypoxia .   niche .   germline stem cells .   self-renewal .   migration .   IGF-1R .   HIF-2α .   OCT4 .   SDF-1 .   CXCR4.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

유료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기