Neuron-to-astrocyte transition: phenotypic fluidity and the formation of hybrid asterons in differentiating neurospheres.
To the extent that their fate choice and differentiation processes can be understood and manipulated, neural stem cells represent a promising therapeutic tool for a variety of neuropathologies. We have previously shown that mature astrocytes possess neural stem cell attributes, and can give rise to neurons through the formation of multipotent neurosphere clones. Here we show that relatively mature neurons generated from neurospheres derived from postnatal subependymal zone or cerebellar cortex undergo a phenotypic transformation into astrocytes that coincides with the appearance of a nonfused, hybrid cell type that shares the morphology, antigenicity, and physiology of both neurons and astrocytes. We refer to this astrocyte/neuron hybrid as an "asteron," and hypothesize that it represents an intermediate step in the trans- or dedifferentiation of neurons into astrocytes. The present finding suggests that seemingly terminally differentiated neural cells may in fact represent points along a bidirectionally fluid continuum of differentiation, with intermediate points represented by "hybrid" cells coexpressing phenotypic markers of more than one lineage.
Laywell
Eric D
ED
Department of Anatomy and Cell Biology, The McKnight Brain Institute, Shands Cancer Center, and Program in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, 32610, USA. elaywell@anatomy.med.ufl.edu
Kearns
Sean M
SM
Zheng
Tong
T
Chen
K Amy
KA
Deng
Jie
J
Chen
Huan-Xin
HX
Roper
Steven N
SN
Steindler
Dennis A
DA
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002525:Cerebellar Cortex / Q000166:cytology* / Q000502:physiology; D002552:Cerebral Ventricles / Q000166:cytology; D002999:Clone Cells / Q000166:cytology / Q000502:physiology; D004805:Ependyma / Q000166:cytology / Q000502:physiology; D005260:Female; D006822:Hybrid Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D018874:Spheroids, Cellular / Q000166:cytology / Q000502:physiology