Cell-intrinsic differences between stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity.
Stem cells in different regions of the nervous system give rise to different types of mature cells. This diversity is assumed to arise in response to local environmental differences, but the contribution of cell-intrinsic differences between stem cells has been unclear. At embryonic day (E)14, neural crest stem cells (NCSCs) undergo primarily neurogenesis in the gut but gliogenesis in nerves. Yet gliogenic and neurogenic factors are expressed in both locations. NCSCs isolated by flow-cytometry from E14 sciatic nerve and gut exhibited heritable, cell-intrinsic differences in their responsiveness to lineage determination factors. Gut NCSCs were more responsive to neurogenic factors, while sciatic nerve NCSCs were more responsive to gliogenic factors. Upon transplantation of uncultured NCSCs into developing peripheral nerves in vivo, sciatic nerve NCSCs gave rise only to glia, while gut NCSCs gave rise primarily to neurons. Thus, cell fate in the nerve was stem cell determined.
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
Suzanne
S
Bixby
Genevieve M
GM
Kruger
Jack T
JT
Mosher
Nancy M
NM
Joseph
Sean J
SJ
Morrison
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D020890:Neuregulin-1 / Q000378:metabolism / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D020890:Neuregulin-1; D020800:Receptor, Nerve Growth Factor; C064045:delta protein