Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact

Sosa, Miguel A. Gama; Gasperi, Rita De; Rocher, Anne B.; Perez, Gissel M.; Simons, Keila; Cruz, Daniel; Hof, Patrick R.; Elder, Gregory A.

doi:10.1038/cr.2007.53

Cited by 41 publications

(23 citation statements)

References 18 publications

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“…In the past, brain endothelial cells have shown to interact with neural stem cells from the central nervous system (CNS) in different ways. In 2007, Sosa et al (2004) showed that depending on the co-culture system, endothelial cells either promote self-renewal of neural stem cells via soluble factors as originally described by Shen et al (2004) or promote neuronal differentiation by direct contact (Shen et al 2004;Gama Sosa et al 2007). To the best of our knowledge, this is the first study where the direct interaction of primary murine ENSc and MVCs was investigated.…”

Section: Figmentioning

confidence: 88%

Vascular and neural stem cells in the gut: do they need each other?

Schrenk

Schuster

Klotz

et al. 2014

Histochem Cell Biol

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Enteric neurons and blood vessels form intricate networks throughout the gastrointestinal tract. To support the hypothesis of a possible interaction of both networks, we investigated whether primary mesenteric vascular cells (MVCs) and enteric nervous system (ENS)-derived cells (ENSc) depend on each other using two- and three-dimensional in vitro assays. In a confrontation assay, both cell types migrated in a target-oriented manner towards each other. The migration of MVCs was significantly increased when cultured in ENSc-conditioned medium. Co-cultures of ENSc with MVCs resulted in an improved ENSc proliferation and differentiation. Moreover, we analysed the formation of the vascular and nervous system in developing mice guts. It was found that the patterning of newly formed microvessels and neural stem cells, as confirmed by nestin and SOX2 stainings, is highly correlated in all parts of the developing gut. In particular in the distal colon, nestin/SOX2-positive cells were found in the tissues adjacent to the capillaries and in the capillaries themselves. Finally, in order to provide evidences for a mutual interaction between endothelial and neural cells, the vascular patterns of a RET((-/-)) knockout mouse model as well as human Hirschsprung's cases were analysed. In the distal colon of postnatal RET((-/-)) knockout mice, the vascular and neural networks were similarly disrupted. In aganglionic zones of Hirschsprung's patients, the microvascular density was significantly increased compared with the ganglionic zone within the submucosa. Taken together, these findings indicate a strong interaction between the enteric nervous and vascular system.

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Section: Figmentioning

confidence: 88%

Vascular and neural stem cells in the gut: do they need each other?

Schrenk

Schuster

Klotz

et al. 2014

Histochem Cell Biol

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“…Primary neuronal cultures were prepared from the cerebral cortex isolated from E15.5-16 embryos as previously described [86,87] and maintained in Neurobasal medium/B27 supplement (Invitrogen) for 5-7 days in vitro (DIV). For treatment with insulin or IGF-1, neurons were maintained overnight in neurobasal medium devoid of B27 supplement and then treated as described above.…”

Section: Methodsmentioning

confidence: 99%

Presenilin-1 regulates induction of hypoxia inducible factor-1α: altered activation by a mutation associated with familial Alzheimer's disease

Gasperi

Sosa

Dracheva

et al. 2010

Mol Neurodegeneration

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BackgroundMutations in presenilin-1 (Psen1) cause familial Alzheimer's disease (FAD). Both hypoxia and ischemia have been implicated in the pathological cascade that leads to amyloid deposition in AD. Here we investigated whether Psen1 might regulate hypoxic responses by modulating induction of the transcription factor hypoxia inducible factor 1-α (HIF-1α).ResultsIn fibroblasts that lack Psen1 induction of HIF-1α was impaired in response to the hypoxia mimetic cobalt chloride, as well as was induction by insulin and calcium chelation. Reintroduction of human Psen1 using a lentiviral vector partially rescued the responsiveness of Psen1-/- fibroblasts to cobalt chloride induction. HIF-1α induction did not require Psen1's associated γ-secretase activity. In addition, the failure of insulin to induce HIF-1α was not explicable on the basis of failed activation of the phosphatidylinositol 3-kinase (PI3K/Akt) pathway which activated normally in Psen1-/- fibroblasts. Rather we found that basal levels of HIF-1α were lower in Psen1-/- fibroblasts and that the basis for lower constitutive levels of HIF-1α was best explained by accelerated HIF-1α degradation. We further found that Psen1 and HIF-1α physically interact suggesting that Psen1 may protect HIF-1α from degradation through the proteasome. In fibroblasts harboring the M146V Psen1 FAD mutation on a mouse Psen1 null background, metabolic induction of HIF-1α by insulin was impaired but not hypoxic induction by cobalt chloride. Unlike Psen1-/- fibroblasts, basal levels of HIF-1α were normal in FAD mutant fibroblasts but activation of the insulin-receptor pathway was impaired. Interestingly, in Psen1-/- primary neuronal cultures HIF-1α was induced normally in response to cobalt chloride but insulin induction of HIF-1α was impaired even though activation of the PI3K/Akt pathway by insulin proceeded normally in Psen1-/- neuronal cultures. Basal levels of HIF-1α were not significantly different in Psen1-/- neurons and HIF-1α levels were normal in Psen1-/- embryos.ConclusionsCollectively these studies show that Psen1 regulates induction of HIF-1α although they indicate that cell type specific differences exist in the effect of Psen1 on induction. They also show that the M146V Psen1 FAD mutation impairs metabolic induction of HIF-1α, an observation that may have pathophysiological significance for AD.

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“…Using cocultures, we found that proliferation and Sox2 expression are increased in SVZ cells in contact with BEC. However, these effects may also be due to diffusible soluble factors, based on the fact that NSCs derived from embryonic and postnatal rodents remain undifferentiated, and proliferate in the presence of EC-derived diffusible cues (Shen et al, 2004; Gama Sosa et al, 2007; Plane et al, 2010; Sun et al, 2010). Therefore, we also determined the proportion of Sox2+ cells and BrdU+ cells in SVZ cells that were not in contact with BEC, but were exposed to EC diffusible factors.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, direct coculture of mouse or human embryonic NSCs with EC increased neuronal differentiation (Mathieu et al, 2006; Gama Sosa et al, 2007; Chintawar et al, 2009). Although there are differences in the developmental status of the cells used in these studies as compared to our cells, the timing of the cocultures may be critical in explaining the apparent discrepancies: indeed we examined neuronal differentiation and commitment at 24 h due to the viability of BEC, while the other studies used later time points (up to 8 days).…”

Section: Discussionmentioning

confidence: 99%

Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and α6β1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties

Rosa

Grade

Santos

et al. 2016

Front. Cell. Neurosci.

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Neurogenesis in the subventricular zone (SVZ) is regulated by diffusible factors and cell–cell contacts. In vivo, SVZ stem cells are associated with the abluminal surface of blood vessels and such interactions are thought to regulate their neurogenic capacity. SVZ neural stem cells (NSCs) have been described to contact endothelial-derived laminin via α6β1 integrin. To elucidate whether heterocellular contacts with brain endothelial cells (BEC) regulate SVZ cells neurogenic capacities, cocultures of SVZ neurospheres and primary BEC, both obtained from C57BL/6 mice, were performed. The involvement of laminin-integrin interactions in SVZ homeostasis was tested in three ways. Firstly, SVZ cells were analyzed following incubation of BEC with the protein synthesis inhibitor cycloheximide (CHX) prior to coculture, a treatment expected to decrease membrane proteins. Secondly, SVZ cells were cocultured with BEC in the presence of an anti-α6 integrin neutralizing antibody. Thirdly, BEC were cultured with β1−/− SVZ cells. We showed that contact with BEC supports, at least in part, proliferation and stemness of SVZ cells, as evaluated by the number of BrdU positive (+) and Sox2+ cells in contact with BEC. These effects are dependent on BEC-derived laminin binding to α6β1 integrin and are decreased in cocultures incubated with anti-α6 integrin neutralizing antibody and in cocultures with SVZ β1−/− cells. Moreover, BEC-derived laminin sustains stemness in SVZ cell cultures via activation of the Notch and mTOR signaling pathways. Our results show that BEC/SVZ interactions involving α6β1 integrin binding to laminin, contribute to SVZ cell proliferation and stemness.

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Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact

Cited by 41 publications

References 18 publications

Vascular and neural stem cells in the gut: do they need each other?

Vascular and neural stem cells in the gut: do they need each other?

Presenilin-1 regulates induction of hypoxia inducible factor-1α: altered activation by a mutation associated with familial Alzheimer's disease

Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and α6β1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties

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