Niche Laminin and IGF-1 Additively Coordinate the Maintenance of Oct-4 Through CD49f/IGF-1R-Hif-2α Feedforward Loop in Mouse Germline Stem Cells

Heng Kien Au, Syue Wei Peng, Chin Lin Guo, Chien Chia Lin, Yi Lin Wang, Yung Che Kuo, Tsz Yau Law, Hong Nerng Ho, Thai Yen Ling, Yen Hua Huang

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism on how extracellular matrix (ECM) cooperates with niche growth factors and oxygen tension to regulate the self-renewal of embryonic germline stem cells (GSCs) still remains unclear. Lacking of an appropriate in vitro cell model dramatically hinders the progress. Herein, using a serum-free culture system, we demonstrated that ECM laminin cooperated with hypoxia and insulin-like growth factor 1 receptor (IGF-1R) to additively maintain AP activity and Oct-4 expression of AP+GSCs. We found the laminin receptor CD49f expression in d2 testicular GSCs that were surrounded by laminin. Laminin and hypoxia significantly increased the GSC stemness-related genes, including Hif-2α, Oct-4, IGF-1R, and CD49f. Cotreatment of IGF-1 and laminin additively increased the expression of IGF-IR, CD49f, Hif-2α, and Oct-4. Conversely, silencing IGF-1R and/or CD49f decreased the expression of Hif-2α and Oct-4. The underlying mechanism involved CD49f/IGF1R-(PI3K/AKT)-Hif-2α signaling loop, which in turn maintains Oct-4 expression, symmetric self-renewal, and cell migration. These findings reveal the additive niche laminin/IGF-IR network during early GSC development.

Original languageEnglish
Article number646644
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - Jul 26 2021

Keywords

  • extracellular matrix
  • germline stem cell
  • hypoxia
  • IGF
  • laminin
  • niche
  • self-renewal

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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