Neurosphere

About: Neurosphere is a research topic. Over the lifetime, 5145 publications have been published within this topic receiving 321088 citations.

Dopamine depletion impairs precursor cell proliferation in Parkinson disease

Abstract: Cerebral dopamine depletion is the hallmark of Parkinson disease. Because dopamine modulates ontogenetic neurogenesis, depletion of dopamine might affect neural precursors in the subependymal zone and subgranular zone of the adult brain. Here we provide ultrastructural evidence showing that highly proliferative precursors in the adult subependymal zone express dopamine receptors and receive dopaminergic afferents. Experimental depletion of dopamine in rodents decreases precursor cell proliferation in both the subependymal zone and the subgranular zone. Proliferation is restored completely by a selective agonist of D2-like (D2L) receptors. Experiments with neural precursors from the adult subependymal zone grown as neurosphere cultures confirm that activation of D2L receptors directly increases the proliferation of these precursors. Consistently, the numbers of proliferating cells in the subependymal zone and neural precursor cells in the subgranular zone and olfactory bulb are reduced in postmortem brains of individuals with Parkinson disease. These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation.

Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.

Abstract: Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by symmetrical divisions In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions Ex vivo expansion of pure populations of tissue stem cells has proven elusive Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS) cells NS cells were derived first from mouse ES cells Neural lineage induction was followed by growth factor addition in basal culture media In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain Colonies generated from single NS cells all produce neurons upon growth factor withdrawal NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain Similar NS cells can be generated from human ES cells and human foetal brain The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation These homogenous cultures will enable delineation of molecular mechanisms that define a tissue-specific stem cell and allow direct comparison with pluripotent ES cells

Variation in the safety of induced pluripotent stem cell lines

Abstract: We evaluated the teratoma-forming propensity of secondary neurospheres (SNS) generated from 36 mouse induced pluripotent stem (iPS) cell lines derived in 11 different ways. Teratoma-formation of SNS from embryonic fibroblast-derived iPS cells was similar to that of SNS from embryonic stem (ES) cells. In contrast, SNS from iPS cells derived from different adult tissues varied substantially in their teratoma-forming propensity, which correlated with the persistence of undifferentiated cells.