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

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.

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Genome-wide analysis of histone acetylation dynamics during mouse embryonic stem cell neural differentiation

Genomics Data ◽

10.1016/j.gdata.2015.05.001 ◽

2015 ◽

Vol 5 ◽

pp. 15-16 ◽

Cited By ~ 3

Author(s):

Pingyu Liu ◽

Xiaoyang Dou ◽

Guangdun Peng ◽

Jing-Dong Jackie Han ◽

Naihe Jing

Keyword(s):

Stem Cell ◽

Embryonic Stem Cell ◽

Histone Acetylation ◽

Neural Differentiation ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Genome Wide Analysis ◽

Genome Wide

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Increase in dopaminergic neurons from mouse embryonic stem cell-derived neural progenitor/stem cells is mediated by hypoxia inducible factor-1α

Journal of Neuroscience Research ◽

10.1002/jnr.21687 ◽

2008 ◽

Vol 86 (11) ◽

pp. 2353-2362 ◽

Cited By ~ 28

Author(s):

Tae-Sun Kim ◽

Sachiyo Misumi ◽

Cha-Gyun Jung ◽

Tadashi Masuda ◽

Yoshiaki Isobe ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Dopaminergic Neurons ◽

Hypoxia Inducible Factor ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cell ◽

Neural Progenitor ◽

Hypoxia Inducible Factor 1Α

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

Stem Cells International ◽

10.1155/2019/4084351 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

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.

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

Stem Cells International ◽

10.1155/2014/379678 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 7

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.

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

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.4639 ◽

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.

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Long Noncoding RNA: Function and Mechanism on Differentiation of Mesenchymal Stem Cells and Embryonic Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666181127145809 ◽

2019 ◽

Vol 14 (3) ◽

pp. 259-267

Author(s):

Jian Zhu ◽

Yitian Wang ◽

Wei Yu ◽

Kaishun Xia ◽

Yuluan Huang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Transcription Regulation ◽

Noncoding Rna ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Differentiation Process ◽

Pathologic Process

Background:Long suspected as transcriptional noise, recently recognized, long non-coding RNAs (lncRNAs) are emerging as an indicator, biomarker and therapy target in the physiologic and pathologic process. Mesenchymal stem cells and embryonic stem cells are important source for normal and therapeutic tissue repair. However, the mechanism of stem cell differentiation is not completely understood. Research on lncRNAs may provide novel insights into the mechanism of differentiation process of the stem cell which is important for the application of stem cell therapy. The lncRNAs field is still very young, new insights into lncRNAs function are emerging to a greater understanding of biological processes. Objective: In this review, we summarize the recent researches studying lncRNAs and illustrate how they act in the differentiation of the mesenchymal stem cells and embryonic stem cells, and discuss some future directions in this field. Results: Numerous lncRNAs were differentially expressed during differentiation of mesenchymal stem cells and embryonic stem cells. LncRNAs were able to regulate the differentiation processes through epigenetic regulation, transcription regulation and post-transcription regulation. Conclusion: LncRNAs are involved in the differentiation process of mesenchymal stem cells and embryonic stem cells, and they could become promising indicator, biomarker and therapeutic targets in the physiologic and pathologic process. However, the mechanisms of the role of lncRNAs still require further investigation.

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

Stroke ◽

10.1161/str.46.suppl_1.tp89 ◽

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.

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