Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.
Stem Cells
; 35(9): 2071-2082, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28733998
ABSTRACT
Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP)- Oct4+ cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP+ NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4fl/fl ;Sox1Cre (Oct4CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP+ dNSCs, in these Oct4CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine ß-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP+ dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;352071-2082.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Envelhecimento
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Ciclo Celular
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Fator 3 de Transcrição de Octâmero
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Células-Tronco Neurais
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Proteína Glial Fibrilar Ácida
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article