Isolation of neural stem cells from the postnatal cerebellum.
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.
Lee
Audra
A
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Kessler
Jessica D
JD
Read
Tracy-Ann
TA
Kaiser
Constanze
C
Corbeil
Denis
D
Huttner
Wieland B
WB
Johnson
Jane E
JE
Wechsler-Reya
Robert J
RJ
D000071916:AC133 Antigen; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D033581:Stem Cell Transplantation; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics
D000071916:AC133 Antigen; D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D006023:Glycoproteins; D053823:Hedgehog Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010455:Peptides; D015534:Trans-Activators; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C000606024:Prom1 protein, mouse