Stem Cells with Neurogenic Potential and Steroid Hormones

Velasco, Iván

doi:10.2174/156802611796117586

Cited by 7 publications

(4 citation statements)

References 102 publications

(136 reference statements)

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“…Glycoproteins and steroid hormones have been reported to regulate different aspects of neurodevelopment and neural stem cell properties, where they usually play neurotrophic roles. 79 , 80 , 81 We found that the FSH pathway was activated by ING5, with ING5 overexpression increasing levels of membrane bound FSH receptors. Blocking the FSH pathway also reduced the ability of BTICs to self-renew.…”

Section: Discussionmentioning

confidence: 79%

ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways

Wang

Chesnelong

et al. 2017

Oncogene

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Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC ‘stemness’ affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations. This activity requires the plant homeodomain region of ING5 that interacts specifically with the H3K4me3 mark. ING5 also enhances PI3K/AKT and MEK/ERK activity to sustain self-renewal of BTICs over serial passage of stem cell-like spheres. ING5 exerts these effects by activating transcription of calcium channel and follicle stimulating hormone pathway genes. In silico analyses of The Cancer Genome Atlas data suggest that ING5 is a positive regulator of BTIC stemness, whose expression negatively correlates with patient prognosis, especially in the Proneural and Classical subtypes, and in tumors with low SOX2 expression. These data suggest that altering histone acetylation status and signaling pathways induced by ING5 may provide useful clinical strategies to target tumor resistance and recurrence in glioblastoma.

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Section: Discussionmentioning

confidence: 79%

ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways

Wang

Chesnelong

et al. 2017

Oncogene

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“…Stem cells with multi differentiation potential for neuronal phenotypes are influenced by steroid hormones, such as regulating gene expression by binding to intracellular steroid receptors, activation of intracellular pathways involving kinases or intracellular calcium signaling, and modulation of receptors for neurotransmitters (reviewed in Velasco, 2011). Interestingly, steroid hormones can even substitute for modulate the action of growth factors and also directly influence self-renewal, proliferation, differentiation, or cell death of neurogenic stem cells.…”

Section: Neurosteroids and Neurosteroidogenic Antidepressants Regulatmentioning

confidence: 99%

Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression

et al. 2011

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The pharmacological action of selective serotonin reuptake inhibitor antidepressants may include a normalization of the decreased brain levels of the brain-derived neurotrophic factor (BDNF) and of neurosteroids such as the progesterone metabolite allopregnanolone, which are decreased in patients with depression and posttraumatic stress disorders (PTSD). The allopregnanolone and BDNF level decrease in PTSD and depressed patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated. Preclinical studies using the socially isolated mouse as an animal model of behavioral deficits, which resemble some of the symptoms observed in PTSD patients, have shown that fluoxetine and derivatives improve anxiety-like behavior, fear responses and aggressive behavior by elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression. These actions appeared to be independent and more selective than the action of these drugs on serotonin reuptake inhibition. Hence, this review addresses the hypothesis that in PTSD or depressed patients, brain allopregnanolone levels, and BDNF expression upregulation may be mechanisms at least partially involved in the beneficial actions of antidepressants or other selective brain steroidogenic stimulant molecules.

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“…Sex steroid hormones participate in many physiological processes, including proliferation of neural precursors, neuronal differentiation or neuroprotection (8–10). Undifferentiated mouse ES cells express progesterone receptor (PR) isoforms A and B, as well as estrogen receptor (ER)‐α and ER‐β (11, 12).…”

Section: Introductionmentioning

confidence: 99%

Progesterone and 17β‐estradiol increase differentiation of mouse embryonic stem cells to motor neurons

2011

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SummaryEmbryonic stem (ES) cells have the capacity to differentiate into endodermal, mesodermal, and ectodermal lineages. Motor neuron (MN) differentiation of mouse ES cells involves embryoid bodies formation with addition of Sonic hedgehog and retinoic acid. In this work, using immunocytochemistry, flow cytometry, and quantitative RT-PCR, we investigated whether progesterone or 17b-estradiol have inductive effects on ES cellderived MN, as it has been demonstrated that these hormones modify proliferation and neural differentiation of pluripotent cells. When 100 nM progesterone was added during differentiation, we found higher proportions of MN, compared to the control condition; coincubation of progesterone with the progesterone receptor (PR) antagonist RU-486 caused a decrease in the number of MN to a percentage even lower than controls. The addition of nanomolar concentrations of 17b-estradiol also significantly induced MN differentiation. This effect of estradiol was completely antagonized by addition of the general estrogen receptor (ER) antagonist ICI 182,780. To identify the ER subtype mediating the increase on MN differentiation, we incubated estradiol with the ER-a antagonist MPP or with the ER-b blocker PHTPP. When we coincubated 17b-estradiol with MPP, we found a significant decrease in the percentage of MN. In contrast, the coincubation of 17b-estradiol with PHTPP had no effect on the induction of MN differentiation. All these effects on cell number were confirmed by significant changes in the expression of the MN markers Islet-1 and Choline acetyl transferase, assessed by real-time RT-PCR. Cell proliferation in embryoid bodies was significantly enhanced by progesterone treatment. No changes in apoptotic cell death were found in differentiating cells after progesterone or 17b-estradiol addition. Our findings indicate that progesterone and 17b-estradiol induce a higher proportion of MN derived from mouse ES cells through intracellular PR and ER, respectively. Furthermore, the effect of estradiol was mediated by specific activation of ER-a.

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Stem Cells with Neurogenic Potential and Steroid Hormones

Cited by 7 publications

References 102 publications

ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways

ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways

Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression

Progesterone and 17β‐estradiol increase differentiation of mouse embryonic stem cells to motor neurons

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