Characteristics of Neural Stem Cells Expanded in Lowered Oxygen and the Potential Role of Hypoxia-Inducible Factor-1Alpha

Zhang, Cuiping; Zhu, Lijing; Zhao, Tong; Zhao, Huiqing; Huang, Xin; Ma, Xin; Wang, Hai; Fan, Ming

doi:10.1159/000103385

Cited by 51 publications

(44 citation statements)

References 20 publications

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“…Cells derived from Wistar rat mesencephalon (E13.5) were mechanically dissociated, and grown in DMEM/F12 (1:1) medium containing 2 mM L-glutamine, 5 IU of penicillin, 5 μg/ml streptomycin (BioWhittaker), 1% N2 (Life Technologies), 1% B27 (Life Technologies), 20 ng/ml epidermal growth factor (EGF; Sigma) and 20 ng/ml basic fibroblast growth factor (bFGF; R&D Systems, Minneapolis, MN; Zhang et al 2007). Cells were plated on plastic 35 mm dishes precoated with poly-L-lycine.…”

Section: Isolation and Culture Of Npcsmentioning

confidence: 99%

Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation of embryonic neural stem/progenitor cells

Xiong

Zhao²,

Huang³

et al. 2009

Cell Stress and Chaperones

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Hypoxia may regulate the proliferation of diverse stem cells. Our previous study showed that hypoxia promoted the proliferation of embryonic neural stem/progenitor cells (NPCs) and that hypoxia inducible factor-1(HIF-1) was critical in this process. HIF-1 could be stabilized under hypoxic conditions, and heat shock protein 90 (HSP90) is an essential protein that controls the activity and stabilization of HIF-1α. In the present work, we investigate whether HSP90 is involved in proliferation of NPCs under hypoxia by regulating HIF-1α stabilization. Geldanamycin (GA), an HSP90 inhibitor, decreased the expression of HIF-1α in NPCs during hypoxia-driven proliferation and reduced the expression level of HIF-1α protein under hypoxia in a time-dependent manner.

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Section: Isolation and Culture Of Npcsmentioning

confidence: 99%

Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation of embryonic neural stem/progenitor cells

Xiong

Zhao²,

Huang³

et al. 2009

Cell Stress and Chaperones

Self Cite

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“…Low atmospheric oxygen levels of 3% confer long-term proliferation and stem cell maintenance of midbrain dopaminergic NPCs in vitro, including the conservation of their dopaminergic differentiation potential, and avoid senescence in various species, including mouse [18][19][20][21][22][23][24]. Further in vitro studies have shown that the oxygen-dependent transcription factor hypoxiainducible factor 1a (HIF-1a) is involved in these processes [15,25,26] and is responsible for the initial adaptive response of cells to oxygen variations [27,28].…”

Section: Introductionmentioning

confidence: 99%

Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain

WagenführLisa

Karen

MarroneLara

et al. 2016

Stem Cells and Development

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Oxygen tension is an important factor controlling stem cell proliferation and maintenance in various stem cell populations with a particular relevance in midbrain dopaminergic progenitors. Further studies have shown that the oxygen-dependent transcription factor hypoxia-inducible factor 1a (HIF-1a) is involved in these processes. However, all available studies on oxygen effects in dopaminergic neuroprogenitors were performed in vitro and thus it remains unclear whether tissue oxygen tension in the embryonic midbrain is also relevant for the regulation of dopaminergic neurogenesis in vivo. We thus dissect here the effects of oxygen tension in combination with HIF-1a conditional knockout on dopaminergic neurogenesis by using a novel experimental design allowing for the control of oxygen tension within the microenvironment of the neurogenic niche of the murine fetal midbrain in vivo. The microenvironment of the midbrain dopaminergic neurogenic niche was detected as hypoxic with oxygen tensions below 1.1%. Maternal oxygen treatment of 10%, 21%, and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal midbrain oxygenation. Fetal midbrain hypoxia hampered the generation of dopaminergic neurons and is accompanied with restricted fetal midbrain development. In contrast, induced hyperoxia stimulated proliferation and differentiation of dopaminergic progenitors during early and late embryogenesis. Oxygen effects were not directly mediated through HIF-1a signaling. These data-in agreement with in vitro data-indicate that oxygen is a crucial regulator of developmental dopaminergic neurogenesis. Our study provides the initial framework for future studies on molecular mechanisms mediating oxygen regulation of dopaminergic neurogenesis within the fetal midbrain as its natural environment.

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“…It is now known that lowered oxygen concentration enhances neurogenesis and delays certain differentiation processes (15,16). For instance, HIF1␣ interacts with Notch1 to maintain undifferentiated cell states (5), whereas HIF2␣ binds to the marker of the undifferentiated state Oct4 promoter, inducing its expression and transcriptional activity (8).…”

mentioning

confidence: 99%

FM19G11, a New Hypoxia-inducible Factor (HIF) Modulator, Affects Stem Cell Differentiation Status

Moreno‐Manzano

Rodríguez‐Jiménez

Acena-Bonilla

et al. 2010

Journal of Biological Chemistry

102

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The biology of the ␣ subunits of hypoxia-inducible factors (HIF␣) has expanded from their role in angiogenesis to their current position in the self-renewal and differentiation of stem cells. The results reported in this article show the discovery of FM19G11, a novel chemical entity that inhibits HIF␣ proteins that repress target genes of the two ␣ subunits, in various tumor cell lines as well as in adult and embryonic stem cell models from rodents and humans, respectively. FM19G11 inhibits at nanomolar range the transcriptional and protein expression of Oct4, Sox2, Nanog, and Tgf-␣ undifferentiating factors, in adult rat and human embryonic stem cells, FM19G11 activity occurs in ependymal progenitor stem cells from rats (epSPC), a cell model reported for spinal cord regeneration, which allows the progression of oligodendrocyte cell differentiation in a hypoxic environment, has created interest in its characterization for pharmacological research. Experiments using small interfering RNA showed a significant depletion in Sox2 protein only in the case of HIF2␣ silencing, but not in HIF1␣-mediated ablation. Moreover, chromatin immunoprecipitation data, together with the significant presence of functional hypoxia response element consensus sequences in the promoter region of Sox2, strongly validated that this factor behaves as a target gene of HIF2␣ in epSPCs. FM19G11 causes a reduction of overall histone acetylation with significant repression of p300, a histone acetyltransferase required as a co-factor for HIF-transcription activation. Arrays carried out in the presence and absence of the inhibitor showed the predominant involvement of epigenetic-associated events mediated by the drug.

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Characteristics of Neural Stem Cells Expanded in Lowered Oxygen and the Potential Role of Hypoxia-Inducible Factor-1Alpha

Cited by 51 publications

References 20 publications

Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation of embryonic neural stem/progenitor cells

Heat shock protein 90 is involved in regulation of hypoxia-driven proliferation of embryonic neural stem/progenitor cells

Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain

FM19G11, a New Hypoxia-inducible Factor (HIF) Modulator, Affects Stem Cell Differentiation Status

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