Survival and differentiation of neuroectodermal cells with stem cell properties at different oxygen levels.
Freeze-lesioned regions of the forebrain cortex provide adequate environment for growth of non-differentiated neural progenitors, but do not support their neuron formation. Reduced oxygen supply, among numerous factors, was suspected to impair neuronal cell fate commitment. In the present study, proliferation and differentiation of neural stem/progenitor cells were investigated at different oxygen levels both in vitro and in vivo. Low (1% atmospheric) oxygen supply did not affect the in vitro viability and proliferation of stem cells or the transcription of "stemness" genes but impaired the viability of committed neuronal progenitors and the expression of proneural and neuronal genes. Consequently, the rate of in vitro neuron formation was markedly reduced under hypoxic conditions. In vivo, neural stem/progenitor cells survived and proliferated in freeze-lesioned adult mouse forebrains, but did not develop into neurons. Hypoperfusion-caused hypoxia in lesioned cortices was partially corrected by hyperbaric oxygen treatment (HBOT). HBOT, while reduced the rate of cell proliferation at the lesion site, resulted in sporadic neuron formation from implanted neural stem cells. The data indicate that in hypoxic brain areas, neural stem cells survive and proliferate, but neural tissue-type differentiation can not proceed. Oxygenation renders the damaged brain areas more permissive for tissue-type differentiation and may help the integration of neural stem/progenitor cells.
Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083 Szigony u. 43, Budapest, Hungary.
Anita
A
Zádori
Viktor Antal
VA
Agoston
Kornél
K
Demeter
Nóra
N
Hádinger
Linda
L
Várady
Tímea
T
Köhídi
Anna
A
Göbl
Zoltán
Z
Nagy
Emília
E
Madarász
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017690:Cell Transplantation / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D006931:Hyperbaric Oxygenation / Q000379:methods; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000601:surgery; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008954:Models, Biological; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D054258:Neural Plate / Q000166:cytology; D046569:Neuroepithelial Cells / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; C497443:Hif1a protein, mouse; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D049452:Green Fluorescent Proteins; D014212:Tretinoin; D010100:Oxygen