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

Cheng C.-L.Yang S.-C.Lai C.-Y.Wang C.-K.Chang C.-F.Lin C.-Y.Chen W.-J.Lin P.-Y.Wu H.-C.Ma N.FRANK LEIGH LULu J.2020-12-082020-12-0820202073-4409https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088675764&doi=10.3390%2fcells9071706&partnerID=40&md5=1be23755037453b8ba5808d800e02821https://scholars.lib.ntu.edu.tw/handle/123456789/524909Human 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.BMAC; BRAK; cell cycle; CXCL14; human embryonic stem cell; IGF-1R; Mip-2γ; self-renewal[SDGs]SDG3alpha chemokine; CXCL14 protein, human; IGF1R protein, human; protein binding; small interfering RNA; somatomedin C receptor; biological model; cell cycle; cell differentiation; cell line; cell self-renewal; cytology; drug effect; gene knockdown; human; human embryonic stem cell; metabolism; signal transduction; Cell Cycle; Cell Differentiation; Cell Line; Cell Self Renewal; Chemokines, CXC; Gene Knockdown Techniques; Human Embryonic Stem Cells; Humans; Models, Biological; Protein Binding; Receptor, IGF Type 1; RNA, Small Interfering; Signal TransductionCXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathwayjournal article10.3390/cells9071706327087302-s2.0-85088675764