scholarly journals Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells

2020 ◽  
Author(s):  
Síle M. Griffin ◽  
Mark R. Pickard ◽  
Clive P. Hawkins ◽  
Adrian C. Williams ◽  
Rosemary A. Fricker
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tyrosine Hydroxylase ◽  
Cell Cultures ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Progenitors ◽  
Neuronal Populations ◽  
Regenerative Therapies

AbstractEmerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action.Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2’-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression.These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.

scholarly journals Epsins Regulate Mouse Embryonic Stem Cell Exit from Pluripotency and Neural Commitment by Controlling Notch Activation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Marina Cardano ◽  
Jacopo Zasso ◽  
Luca Ruggiero ◽  
Giuseppina Di Giacomo ◽  
Matteo Marcatili ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Notch Signaling ◽  
Neural Differentiation ◽  
Radial Glia ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Progenitors ◽  
Notch Activation

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells. Finally, we provide evidence that Notch signaling is impaired following epsin1/2 knockdown and that experimental restoration of Notch signaling rescues the epsin-mediated phenotypes. We conclude that epsins contribute to control mESC exit from pluripotency and allow their neural differentiation by appropriate modulation of Notch signaling.

scholarly journals Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures

2011 ◽  
Vol 89 (9) ◽  
pp. 1363-1374 ◽  
Author(s):  
Megumi Hirose ◽  
Pawel Niewiadomski ◽  
Gary Tse ◽  
Gloria C. Chi ◽  
Hongmei Dong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Motor Neuron ◽  
Adenylyl Cyclase ◽  
Cell Cultures ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell

scholarly journals Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Sarina Ravens ◽  
Marjorie Fournier ◽  
Tao Ye ◽  
Matthieu Stierle ◽  
Doulaye Dembele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Regulation ◽  
Histone Acetyltransferase ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Individual Contribution ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
The Individual

The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation.

scholarly journals Effects of Oxidative Stress on Mouse Embryonic Stem Cell Proliferation, Apoptosis, Senescence, and Self-Renewal

2010 ◽  
Vol 19 (9) ◽  
pp. 1321-1331 ◽  
Author(s):  
Yan-Lin Guo ◽  
Samujjwal Chakraborty ◽  
Suja S. Rajan ◽  
Rouxing Wang ◽  
Faqing Huang
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Self Renewal ◽  
Stem Cell Proliferation

scholarly journals Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Mora-Castilla ◽  
Juan R. Tejedo ◽  
Rafael Tapia-Limonchi ◽  
Irene Díaz ◽  
Ana B. Hitos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Directed Differentiation ◽  
Lineage Differentiation ◽  
Induction Of Differentiation ◽  
Differentiating Agent ◽  
Pluripotency Genes

The function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoderm markers following induction of differentiation with DETA/NO-based protocols. Confocal analysis of cells undergoing directed differentiation shows that the majority of cells expressing Nanog express also endoderm genes such as Gata4 and FoxA2 (75.4% and 96.2%, resp.). Simultaneously, mRNA of mesodermal markers Flk1 and Mef2c are also regulated by the treatment. Acetylated histone H3 occupancy at the promoter of Nanog is involved in the process of reexpression. Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.

scholarly journals Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

2020 ◽  
Author(s):  
Nur Izzati Mansor ◽  
Carolindah Makena Ntimi ◽  
Noraishah Mydin Abdul-Aziz ◽  
King-Hwa Ling ◽  
Aishah Adam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Cells ◽  
Aβ Peptides ◽  
Intracellular Ros

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer’s disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Ab peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies (EBs) in the absence of leukemia inhibitory factor (LIF), followed by the addition of all-trans retinoic acid (ATRA) as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular ROS production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.

Abstract T P89: Curcumin Encapsulated Stem Cell Exosomes Attenuate Ischemic Brain Injury in Type 1 Diabetic Akita Mice

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Anuradha Kalani ◽  
Pradip K Kamat ◽  
Neetu Tyagi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cognitive Functions ◽  
Infarct Volume ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Auditory Brainstem ◽  
Brainstem Response ◽  
Akita Mice

Background and Purpose: Stroke in type-1 diabetes mellitus (T1DM) is severe in terms of exacerbated brain damage and severe functional decline as compared to non-diabetic stroke. Curcumin possesses remarkable medicinal properties and stem cells exosomes (nano-vesicles; 40-100 nm) have paracrine effects with neovascularization properties. The therapy available for stroke (tissue plasminogen activator) is not effective in diabetic stroke and leads to excessive vasodilation and hemorrhagic transformations. Therefore, we tested the hypothesis that encapsulating curcumin to mouse embryonic stem cell exosomes mitigates type-1 diabetic stroke injury. Methods: We employed 8-10 weeks old male genetic T1DM Ins2+/- Akita mice. Ischemia was performed for 40 min and reperfusion for 7 days in the following mice groups: 1) Sham Akita , 2) Sham Akita + cur-exo , 3) IR Akita , 4) IR Akita + cur-exo . Exosomes were isolated from mouse embryonic stem cells culture conditioned media and encapsulated with curcumin ( cur-exo ). Therapeutic exo-cur units were used for mice treatment intranasally for 7 days. Brain cryo-sections were analyzed for vascular (VCAM, VE-cadherin), glial (GFAP), neuronal (Tuj1, nNOS) coupling in ipsilateral area. Neuronal loss, neurodegeneration was analyzed with NeuN, fluorojade-C staining. White matter damage was examined with luxol fast blue. Intra-carotid FITC-BSA infusion was used to assess venular leakage. Passive avoidance and auditory brainstem response tests were used to determine cognitive functions. Results: Treatment with cur-exo alleviated Infarct volume, edema, and vascular damage in IR Akita + cur-exo mice as compared to IR Akita mice. The axonal-glia damage and venular permeability were exacerbated in IR Akita mice, as compared to sham Akita , which were mitigated after cur-exo treatment. Cur-exo also ameliorated neurodegeneration and promoted neuronal survival as determined through immunolocalization studies. Further, cur-exo remarkably restored cognitive functions (p<0.001, n=6). Conclusion: Our results suggested that combining the therapeutic efficacy of curcumin and stem cells exosomes represent a novel treatment for stroke during T1DM. Acknowledgement: This work was supported by NIH grant HL107640.

scholarly journals The establishment of mouse embryonic stem cell cultures on 96-well plates for high-throughput screening

2013 ◽  
Vol 35 (5) ◽  
pp. 456-461 ◽  
Author(s):  
Meeyoung Cho ◽  
Tae-Jun Cho ◽  
Jeong Mook Lim ◽  
Gene Lee ◽  
Jaejin Cho
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Cultures ◽  
High Throughput ◽  
High Throughput Screening ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell
Sign in / Sign up

Export Citation Format

Share Document