Neural Crest Stem Cells Persist in the Adult Gut but Undergo Changes in Self-Renewal, Neuronal Subtype Potential, and Factor Responsiveness

• Published in: Neuron (Cambridge, Mass.) Mass.), 2002-08, Vol.35 (4), p.657-669
• Main Authors: Kruger, Genevieve M., Mosher, Jack T., Bixby, Suzanne, Joseph, Nancy, Iwashita, Toshihide, Morrison, Sean J.
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Animals; Bone Morphogenetic Proteins - metabolism; Bone Morphogenetic Proteins - pharmacology; Catecholamines - biosynthesis; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Lineage - drug effects; Cell Lineage - physiology; Cells, Cultured; Digestive System - cytology; Digestive System - embryology; Digestive System - innervation; Enteric Nervous System - cytology; Enteric Nervous System - embryology; Enteric Nervous System - metabolism; Fetus; Fibroblasts - cytology; Fibroblasts - metabolism; Flow Cytometry; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Intracellular Signaling Peptides and Proteins; Membrane Proteins - metabolism; Membrane Proteins - pharmacology; Mitosis - drug effects; Mitosis - genetics; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Neural Crest - cytology; Neural Crest - embryology; Neural Crest - metabolism; Neuroglia - cytology; Neuroglia - metabolism; Neurons; Neurons - cytology; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Nerve Growth Factor - metabolism; Serotonin - biosynthesis; Stem cells; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(02)00827-9

We found neural crest stem cells (NCSCs) in the adult gut. Postnatal gut NCSCs were isolated by flow-cytometry and compared to fetal gut NCSCs. They self-renewed extensively in culture but less than fetal gut NCSCs. Postnatal gut NCSCs made neurons that expressed a variety of neurotransmitters but lost the ability to make certain subtypes of neurons that are generated during fetal development. Postnatal gut NCSCs also differed in their responsiveness to lineage determination factors, affecting cell fate determination in vivo and possibly explaining their reduced neuronal subtype potential. These perinatal changes in gut NCSCs parallel perinatal changes in hematopoietic stem cells, suggesting that stem cells in different tissues undergo similar developmental transitions. The persistence of NCSCs in the adult PNS opens up new possibilities for regeneration after injury or disease.