CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway

Chih Lun Cheng, Shang Chih Yang, Chien Ying Lai, Cheng Kai Wang, Ching Fang Chang, Chun Yu Lin, Wei Ju Chen, Po Yu Lin, Han Chung Wu, Nianhan Ma, Frank Leigh Lu, Jean Lu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction.

Original languageEnglish
JournalCells
Volume9
Issue number7
DOIs
StatePublished - 16 Jul 2020

Keywords

  • BMAC
  • BRAK
  • CXCL14
  • IGF-1R
  • Mip-2γ
  • cell cycle
  • human embryonic stem cell
  • self-renewal

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