Abstract
The cerebellum is critical for motor coordination and cognitive function and is the target of transformation in medulloblastoma, the most common malignant brain tumor in children. Although the development of granule cells, the most abundant neurons in the cerebellum, has been studied in detail, the origins of other cerebellar neurons and glia remain poorly understood. Here we show that the murine postnatal cerebellum contains multipotent neural stem cells (NSCs). These cells can be prospectively isolated based on their expression of the NSC marker prominin-1 (CD133) and their lack of markers of neuronal and glial lineages (lin-). Purified prominin+ lin- cells form self-renewing neurospheres and can differentiate into astrocytes, oligodendrocytes and neurons in vitro. Moreover, they can generate each of these lineages after transplantation into the cerebellum. Identification of cerebellar stem cells has important implications for the understanding of cerebellar development and the origins of medulloblastoma.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
AC133 Antigen
-
Animals
-
Animals, Newborn
-
Antigens, CD
-
Astrocytes / cytology
-
Astrocytes / metabolism
-
Basic Helix-Loop-Helix Transcription Factors
-
Biomarkers / metabolism
-
Cell Differentiation / drug effects
-
Cell Differentiation / physiology*
-
Cell Lineage / drug effects
-
Cell Lineage / physiology
-
Cell Separation
-
Cerebellum / cytology*
-
Cerebellum / metabolism
-
Cerebellum / physiology*
-
Glycoproteins / genetics
-
Glycoproteins / metabolism*
-
Hedgehog Proteins
-
Interneurons / cytology
-
Interneurons / metabolism*
-
Medulloblastoma / genetics
-
Medulloblastoma / metabolism
-
Medulloblastoma / physiopathology
-
Mice
-
Mice, Transgenic
-
Multipotent Stem Cells / cytology
-
Multipotent Stem Cells / drug effects
-
Multipotent Stem Cells / metabolism*
-
Nerve Growth Factors / metabolism
-
Nerve Growth Factors / pharmacology
-
Nerve Tissue Proteins / metabolism
-
Neuroglia / cytology
-
Neuroglia / metabolism*
-
Oligodendroglia / cytology
-
Oligodendroglia / metabolism
-
Peptides / genetics
-
Peptides / metabolism*
-
Spheroids, Cellular / cytology
-
Spheroids, Cellular / drug effects
-
Spheroids, Cellular / metabolism
-
Stem Cell Transplantation
-
Trans-Activators / metabolism
-
Trans-Activators / pharmacology
-
Transcription Factors / genetics
Substances
-
AC133 Antigen
-
Antigens, CD
-
Atoh1 protein, mouse
-
Basic Helix-Loop-Helix Transcription Factors
-
Biomarkers
-
Glycoproteins
-
Hedgehog Proteins
-
Nerve Growth Factors
-
Nerve Tissue Proteins
-
Peptides
-
Prom1 protein, mouse
-
Trans-Activators
-
Transcription Factors