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.
Highlights
Human embryonic stem cells, isolated from the inner cell mass of blastocysts, are widely known for their unique abilities for unlimited self-renewal and pluripotency [1,2]
We found that CXCL14, a chemokine secreted by Human embryonic stem cells (hESCs), can mediate the self-renewal of hESCs
By comparing the undifferentiated and differentiated hESCs, we first checked the differentiation state by analyzing the mRNA expression levels of the crucial self-renewal marker OCT4 which were downregulated in embryonic body (EB) (Figure 1A)
Summary
Human embryonic stem cells (hESCs), isolated from the inner cell mass of blastocysts, are widely known for their unique abilities for unlimited self-renewal and pluripotency [1,2]. These two important potentials enable hESCs to generate vast quantities of multiple different tissue cells (except placental cells), which sheds substantial light on regenerative medicine and stem cell biology [3,4]. Cytokines can establish an extensive microenvironment to support the properties of hESCs [8,9,10]. Studies of hESC-secreted cytokines and their mechanisms require further exploration
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