Editorial: 2013—A Year of Clinical Success and Great Scientific Innovation in the Stem Cell Field

Nolta, Jan A.

doi:10.1002/stem.1602

Cited by 4 publications

(8 citation statements)

References 18 publications

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“…01; N = 6) ( Fig 3B ). These observations are consistent with our previous report showing that in cultured neuron stem cells, morphine decreases the percentage of immature neurons such as beta-tubulin 3(TUJ-1) positive cells in neural stem cell cultures, but it increases the percentage of GFAP-expressing glia [ 24 ].…”

Section: Resultssupporting

confidence: 93%

“…An alternative explanation for the negative effect on adult neurogenesis is that morphine alters the fate of early progenitors indirectly, inducing more neural stem cell differentiation into glia rather than neurons. Our recent in vitro study with the isolated progenitor cells from the mouse hippocampus indicates that morphine alters the lineage of the progenitors during differentiation by regulating the Prox1/Notch1 pathway via the drug’s control of miR-181a [ 24 ]. Similar results were observed with our current in vivo study.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, a probable mechanism for morphine’s inhibition on adult neurogenesis is the drug regulation of progenitor cells’ differentiation of immature neurons via its control of NeuroD1 activity. Our recent in vitro studies in isolated hippocampal progenitor cells suggest that by regulating Prox1/Notch1 activities via its control of the miR181a level, morphine alters the cell lineage of the progenitor cells during differentiation, favoring the differentiation into glia instead of neurons [ 24 ]. Whether the in vivo effects of morphine are similar to in vitro observations remains to be demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

Zhang

Zheng

et al. 2016

PLoS ONE

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The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine’s inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3–28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

Zhang

Zheng

et al. 2016

PLoS ONE

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“…Coculture of HSCs with M2‐AKT cells resulted in the expansion of phenotypically defined HSCs, but these expanded HSCs were dysfunctional as assessed by both, in vitro and in vivo assays. MSCs are being used in regenerative medicine for various hematological and nonhematological conditions . Our data suggest that it may be important to examine whether the signaling mechanisms prevailing in these cells affect the outcome of the therapy.…”

Section: Discussionmentioning

confidence: 95%

AKT Signaling Prevailing in Mesenchymal Stromal Cells Modulates the Functionality of Hematopoietic Stem Cells via Intercellular Communication

et al. 2016

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The AKT pathway plays an important role in various aspects of stem cell biology. However, the consequences of constitutive activation of AKT in mesenchymal stromal cells (MSCs) on the fate of hematopoietic stem cells (HSCs) were unknown. Here, we show that bone marrow-derived MSCs expressing a constitutively active AKT1 expand HSCs, but severely affect their functionality. Conversely, stromal cells with silenced AKT1 limit HSC proliferation, but boost their functionality. These effects were related to differential modulation of several important regulatory genes, in both, the cocultured HSCs and in the stromal cells themselves. The detrimental effect of stromal cells with constitutively activated AKT1 involved dynamin-dependent endocytosis, whereas the salutary effect of stromal cells devoid of AKT1 was mediated via GAP junctions. Constitutive activation of AKT1 led to deregulated formation of GAP junctions in the stromal cells, which consequently exhibited strikingly increased intercellular transfer of molecular cargo to the HSCs. Conversely, stromal cells with silenced AKT1 exhibited normal intercellular arrangement of GAP junctions at appositional membrane areas, and did not show aberrant intercellular transfer. Micro-vesicles isolated from conditioned media of the stromal cells not only mimicked the effect of these cells, but also showed stronger effects. This is perhaps the first report demonstrating that AKT1 signaling prevailing in the MSCs regulates HSC functionality through various intercellular communication mechanisms. These findings could have important implications in the use of MSCs in regenerative medicine. STEM CELLS 2016;34:2354-2367 SIGNIFICANCE STATEMENTThis study demonstrates that AKT1 signaling prevailing in the mesenchymal stromal cells regulates HSC functionality through various intercellular communication mechanisms. These findings may also have implications in the use of mesenchymal stromal cells in regenerative medicine.

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“…YB-1 is overexpressed in breast cancer, especially in the aggressive triple-negative (TNBC) subtypes, almost 70% of which are strongly positive for YB-1 [ 10 ]. Davies and coworkers [ 14 ] elegantly showed that YB-1 contributes to the conversion of hormone receptor-positive breast cancer cells to the TNBC phenotype.…”

Section: Introductionmentioning

confidence: 99%

Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells

et al. 2015

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Epithelial to mesenchymal transition (EMT) induces cell plasticity and promotes metastasis. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) and the pleiotropic cytokine interleukin 6 (IL-6) have both been implicated in tumor cell metastasis and EMT, but via distinct pathways. Here, we show that direct interplay between YB-1 and IL-6 regulates breast cancer metastasis. Overexpression of YB-1 in breast cancer cell lines induced IL-6 production while stimulation with IL-6 increased YB-1 expression and YB-1 phosphorylation. Either approach was sufficient to induce EMT features, including increased cell migration and invasion. Silencing of YB-1 partially reverted the EMT and blocked the effect of IL-6 while inhibition of IL-6 signaling blocked the phenotype induced by YB-1 overexpression, demonstrating a clear YB-1/IL-6 interdependence. Our findings describe a novel signaling network in which YB-1 regulates IL-6, and vice versa, creating a positive feed-forward loop driving EMT-like metastatic features during breast cancer progression. Identification of signaling partners or pathways underlying this co-dependence may uncover novel therapeutic opportunities.

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Editorial: 2013—A Year of Clinical Success and Great Scientific Innovation in the Stem Cell Field

Cited by 4 publications

References 18 publications

Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

AKT Signaling Prevailing in Mesenchymal Stromal Cells Modulates the Functionality of Hematopoietic Stem Cells via Intercellular Communication

Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells

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