Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body

• Published in: Cell reports (Cambridge) 2017-04, Vol.19 (3), p.471-478
• Main Authors: Annese, Valentina, Navarro-Guerrero, Elena, Rodríguez-Prieto, Ismael, Pardal, Ricardo
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - drug effects; Adult Stem Cells - physiology; angiogenesis and neurogenesis; Animals; Blood Vessels - cytology; Carotid Body - cytology; carotid body physiology; Cell Differentiation - drug effects; Cell Hypoxia - drug effects; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Erythropoietin - pharmacology; Female; hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Male; Mammals - metabolism; Mice, Transgenic; Multipotent Stem Cells - cytology; Multipotent Stem Cells - drug effects; Multipotent Stem Cells - metabolism; Neovascularization, Physiologic - drug effects; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - physiology; neural-crest-derived adult stem cell plasticity and multipotency; Neurogenesis - drug effects; Neuronal Plasticity - drug effects
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.03.065

Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. [Display omitted] •Adult carotid body stem cells display multipotency during organ adaptation to hypoxia•Neural-crest-derived stem cells contribute to angiogenesis in the adult carotid body•Endothelial differentiation from carotid body stem cells is HIF2α and EPO dependent Annese et al. find that neural-crest-derived stem cells residing in the adult carotid body are multipotent. These cells have the capacity to contribute to both neurogenesis and angiogenesis during organ acclimatization to hypoxia. Endothelial fate specification is achieved by intrinsic (HIF2α) and extrinsic (EPO) mechanisms.