Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes

Pistollato, Francesca; Chen, Huiling; Schwartz, Philip H.; Basso, Giuseppe; Panchision, David M.

doi:10.1016/j.mcn.2007.04.003

Cited by 141 publications

(151 citation statements)

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“…Additionally, under basal conditions, significantly more NPCs were generated at 3% than at 20% O 2 , with a greater proportion of viable cells; a finding consistent with a previous study based on feeder and matrigel-maintained human ES cells, reporting a decrease in parthanatic cell death in neurectoderm derived at 3% O 2 . 10 In agreement with the studies on mouse ES cells 7 and cortical NSCs, 8,9 the addition of NAC to neuralising conditions at 20% O 2 could partly reproduce the beneficial effect of low O 2 , suggesting that ROS contribute to cell death during neural conversion. Furthermore, 3% O 2 did not prevent or delay neuronal or glial differentiation of hESC-NPCs, and in particular, the speed of electrophysiological maturation of neurons was remarkably similar in both the low and high oxygen environments.…”

Section: Discussionsupporting

confidence: 84%

“…5 However, significant cell death is observed under such serum-free, defined conditions. 6 The mechanism through which the cells die involves both apoptotic and parthanatic pathways, [6][7][8][9][10] accompanied by the generation of reactive oxygen species (ROS). 10 Consequently, neuralisation protocols often contain antioxidants, which may increase the propensity to accumulate genetic mutations, or involve co-culture with stromal feeder layers.…”

mentioning

confidence: 99%

“…[7][8][9][10]12,[17][18][19][20][21][22][23][24][25][26][27] Furthermore, oxygen has been proposed to act as a developmental morphogen; 24 low oxygen promotes tyrosine hydroxylase positive dopaminergic neurons from midbrain neural precursor cells (NPCs) and oligodendrocyte differentiation from human fetal NPCs. 9,18,23 In addition, oxygen tension is thought to be tightly regulated in the stem cell niche and it is thought that changes in the partial pressure of oxygen (pO 2 ) contribute to the mobilisation of stem cells in an injury response. [25][26][27] In view of the importance of low pO 2 in maintenance of pluripotency, mediated in part through Notch signalling and upregulation of Oct-4, it remains unclear as to whether low O 2 interferes with both neural conversion of hESCs and subsequent neuronal differentiation of hESC-derived NPCs.…”

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Derivation of neural precursor cells from human ES cells at 3% O2 is efficient, enhances survival and presents no barrier to regional specification and functional differentiation

et al. 2011

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In vitro stem cell systems traditionally employ oxygen levels that are far removed from the in vivo situation. This study investigates whether an ambient environment containing a physiological oxygen level of 3% (normoxia) enables the generation of neural precursor cells (NPCs) from human embryonic stem cells (hESCs) and whether the resultant NPCs can undergo regional specification and functional maturation. We report robust and efficient neural conversion at 3% O 2 , demonstration of tri-lineage potential of resultant NPCs and the subsequent electrophysiological maturation of neurons. We also show that NPCs derived under 3% O 2 can be differentiated long term in the absence of neurotrophins and can be readily specified into both spinal motor neurons and midbrain dopaminergic neurons. Finally, modelling the oxygen stress that occurs during transplantation, we demonstrate that in vitro transfer of NPCs from a 20 to 3% O 2 environment results in significant cell death, while maintenance in 3% O 2 is protective. Together these findings support 3% O 2 as a physiologically relevant system to study stem cell-derived neuronal differentiation and function as well as to model neuronal injury.

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Section: Discussionsupporting

confidence: 84%

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confidence: 99%

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confidence: 99%

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Derivation of neural precursor cells from human ES cells at 3% O2 is efficient, enhances survival and presents no barrier to regional specification and functional differentiation

et al. 2011

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“…In addition, near-physiological oxygen tensions (5-6%) improve the efficiency of induced pluripotent stem cell generation (79). Several studies on in vitro differentiation of neural stem cells have shown that low oxygen levels promote proliferation, survival and multipotency as compared to normoxic oxygen levels (80)(81)(82)(83)(84)(85)(86). Hematopoietic stem cells (HSCs) in the bone marrow have been proposed to exist in a low oxygen milieu (87,88).…”

Section: Hypoxia and The Stem Cell Phenotypementioning

confidence: 99%

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Mohlin

Wigerup

Påhlman

2011

Seminars in Cancer Biology

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Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.Mohlin, Sofie; Wigerup, Caroline; Påhlman, Sven Link to publication Citation for published version (APA): Mohlin, S., Wigerup, C., & Påhlman, S. (2011). Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Seminars in Cancer Biology, 21(4), 276-282. DOI: 10.1016276-282. DOI: 10. /j.semcancer.2011 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Neural crest and development of the sympathetic nervous systemThe sympathetic nervous system (SNS) originates from the neural crest, an ephemeral structure during vertebrate development. Located along the neural fold, cells on the neural tube in the ectoderm give rise to the neural crest, in turn generating different derivatives, such as the cranial, hindbrain, vagal and trunk neural crest (reviewed in (9)). Trunk neural crest cells migrate from the neural tube along two defined routes, with one group of cells migrating early along a ventral pathway, giving rise to glial cells and neurons, whereas a later migrating group of cells follows a lateral pathway and gives rise to melanocytes in the skin (10, 11). These mutations were rare in all four studies indicating locus heterogeneity for predisposition of inherited disease, but still demonstrated the importance of the PHOX2B gene in neuroblastoma oncogenesis and initiation (Fig. 1) (58), and Fig. 1). Neuroblastoma differentiation stage and clinical outcomeThere is a well-documented difference in aggressive behavior between the morphologically undifferentiated (neuroblastoma proper) and the differentiated (ganglioneuroblastoma, Cellular adaptation to hypoxiaThe biological consequences of hypoxia involve induced angiogenesis, a switch in glucose metabolism and increased invasion and migration capacities, changes that stimulate tumor progression. The hypoxic response is mainly mediated by stabilization of the hypoxia inducible factor (HIF) proteins. HIFs are heterodimeric transcription factors composed of an oxygen sensitive  subunit and a constitutively expressed  subunit. At physiological oxygen levels, the  subunit is hydroxylated by the oxygen-dependent prolyl hydroxylases (PHDs), leading to interaction with the von Hippel Lindau-ubiquitin ligase complex, followed by ubiquitination and proteasomal degradation. At hypoxia, the PHDs are inactive leading to the 9 stabilization of the HIF- subunits, and by dimerization with the  subunit the comple...

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“…Characterization of the newly forming brown adipocyte‐like cells suggests they utilize metabolism to regulate oxygen tension within the micro‐environment and also express vascular growth factors. Regulation of oxygen tension in the microenvironment is critical during HO not only for chondrogenesis [Zuscik et al, 2008] and neurogenesis [Pistollato et al, 2007], both of which require an hypoxic microenvironment, but also for extensive vascularization, which requires normoxia [Joyal et al, 2011]. The presence of vasorepulsive force originating from significantly hypoxic areas has also been proposed [Joyal et al, 2011] and these forces may also be operative during HO.…”

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confidence: 99%

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

Davis

Salisbury

Olmsted-Davis

et al. 2015

J of Cellular Biochemistry

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Heterotopic ossification (HO) is the de novo formation of bone that occurs in soft tissue, through recruitment, expansion, and differentiation of multiple cells types including transient brown adipocytes, osteoblasts, chondrocytes, mast cells, and platelets to name a few. Much evidence is accumulating that suggests changes in metabolism may be required to accomplish this bone formation. Recent work using a mouse model of heterotopic bone formation reliant on delivery of adenovirus‐transduced cells expressing low levels of BMP2 showed the immediate expansion of a unique brown adipocyte‐like cell. These cells are undergoing robust uncoupled oxidative phosphorylation to a level such that oxygen in the microenvironment is dramatically lowered creating areas of hypoxia. It is unclear how these oxygen changes ultimately affect metabolism and bone formation. To identify the processes and changes occurring over the course of bone formation, HO was established in the mice, and tissues isolated at early and late times were subjected to a global metabolomic screen. Results show that there are significant changes in both glucose levels, as well as TCA cycle intermediates. Additionally, metabolites necessary for oxidation of stored lipids were also found to be significantly elevated. The complete results of this screen are presented here, and provide a unique picture of the metabolic changes occurring during heterotopic bone formation. J. Cell. Biochem. 117: 1044–1053, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

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Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes

Cited by 141 publications

References 80 publications

Derivation of neural precursor cells from human ES cells at 3% O2 is efficient, enhances survival and presents no barrier to regional specification and functional differentiation

Derivation of neural precursor cells from human ES cells at 3% O2 is efficient, enhances survival and presents no barrier to regional specification and functional differentiation

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification

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